A Double-blinded, Randomised, Four-period Crossover Euglycemic Clamp Trial Investigating the Dose-response and Dose-exposure Relationship of BioChaperone Insulin Lispro in Three Different Doses in Subjects With Type 1 Diabetes

Study Overview
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Brief Summary
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The addition of BioChaperone to insulin lispro may accelerate the onset and shorten the duration of action of insulin lispro due to facilitation of the absorption of the insulin after subcutaneous injection. The aim of the trial is to investigate the dose-response and the dose-exposure relationships of BioChaperone insulin lispro under 3 doses, to compare the pharmacokinetics and glucodynamic action of BioChaperone insulin lispro at 0.2U/Kg with Humalog® at 0.2 U/Kg and to assess safety and tolerability of BioChaperone insulin lispro and Humalog®. This is a double-blinded, randomised, four-period crossover phase 2 trial using automated 12-hour euglycemic clamps in subject with type 1 diabetes mellitus. Each subject will be randomly allocated to a sequence of 4 treatments, i.e. with one of three single doses of BioChaperone insulin lispro (0.1, 0.2 and 0.4 U/Kg) or one single dose of Humalog® (0.2 U/Kg) on 4 separate dosing visits.

Official Title
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A Double-blinded, Randomised, Four-period Crossover Euglycemic Clamp Trial Investigating the Dose-response and Dose-exposure Relationship of BioChaperone Insulin Lispro in Three Different Doses in Subjects With Type 1 Diabetes

Conditions
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Diabetes Mellitus Type 1

Intervention / Treatment
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* Drug: BioChaperone insulin lispro 0.2U/Kg
* Drug: BioChaperone insulin lispro 0.1U/Kg
* Drug: BioChaperone insulin lispro 0.4U/Kg
* Drug: Humalog®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes mellitus for at least 12 months Treated with multiple daily insulin injections of insulin pump for at least 12 months Body Mass Index (BMI): 18.5-28.0 Kg.m² Exclusion Criteria: Type 2 diabetes mellitus Receipt of any investigational product within 3 months prior first dosing 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 tobacco or nicotine-contained product within 1 year prior to screening Blood or plasma donation in the past month or more than 500ml within 3 months 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 insulin lispro 0.2U/Kg<br>BioChaperone insulin lispro 0.2U/Kg | Drug: BioChaperone insulin lispro 0.2U/Kg<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.1U/Kg<br>* Single dose of 0.1U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.4U/Kg<br>* Single dose of 0.4U/Kg body weight injected subcutaneously<br>Drug: Humalog®<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>|
| Experimental: BioChaperone insulin lispro 0.1U/Kg<br>BioChaperone insulin lispro 0.1U/Kg | Drug: BioChaperone insulin lispro 0.2U/Kg<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.1U/Kg<br>* Single dose of 0.1U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.4U/Kg<br>* Single dose of 0.4U/Kg body weight injected subcutaneously<br>Drug: Humalog®<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>|
| Experimental: BioChaperone insulin lispro 0.4U/Kg<br>BioChaperone insulin lispro 0.4U/Kg | Drug: BioChaperone insulin lispro 0.2U/Kg<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.1U/Kg<br>* Single dose of 0.1U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.4U/Kg<br>* Single dose of 0.4U/Kg body weight injected subcutaneously<br>Drug: Humalog®<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>|
| Active Comparator: Humalog® 0.2U/Kg<br>Humalog® 0.2U/Kg | Drug: BioChaperone insulin lispro 0.2U/Kg<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.1U/Kg<br>* Single dose of 0.1U/Kg body weight injected subcutaneously<br>Drug: BioChaperone insulin lispro 0.4U/Kg<br>* Single dose of 0.4U/Kg body weight injected subcutaneously<br>Drug: Humalog®<br>* Single dose of 0.2U/Kg body weight injected subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucodynamic endpoint: Area Under the Curve GIR(0-last) | Area under the Glucose Infusion Rate time curve from 0 hours until the end of the clamp | 12 hours | 
| Glucodynamic endpoint: GIRMax | Maximum Glucose Infusion Rate | 12 hours | 
| Pharmacokinetic endpoint: AUC Lisp(0-last) | Area under the insulin lispro serum concentration - time curve over the clamp procedure. | 12 hours | 
| Pharmacokinetic endpoint: Cmax(Lisp) | Maximum observed serum insulin lispro concentration | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Tmax(lisp) | Time to maximum observed serum insulin lispro concentration | 12 hours | 
| Glucodynamic: TGIRmax | Time to maximum Glucose Infusion Rate | 12 hours | 
| Tonset of action | Time from t=0 until blood glucose concentration has decreased by 5mg.dL (0.3mmol.L) from baseline. | 12 hours | 
| Safety and Tolerability: adverse events, local tolerability, vital signs variations, ECG, laboratory safety parameters. |  | 12 weeks |