A Trial to Evaluate the Pharmacokinetic and Pharmacodynamic Properties of BioChaperone® Insulin Lispro, Fiasp® and NovoRapid® Delivered by an Insulin Pump

Study Overview
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Brief Summary
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This is a single-centre, randomised, double-blind, three-period, complete cross-over trial comparing the pharmacokinetic and the pharmacodynamic properties of BioChaperone® insulin lispro and the two active comparators Fiasp® and Novorapid® when given as a bolus on top of basal delivery with an insulin pump in subjects with type 1 diabetes mellitus. Each subject will be randomly assigned to a treatment sequence consisting of 3 dosing visits during which the subject will receive the investigational products. In a euglycaemic clamp setting, subjects will be given a bolus dose of 0.15 U/kg body weight. Throughout the glucose clamp procedure, blood glucose will be stabilised at a target level of 100 mg/dL by means of an intravenous infusion of glucose. Blood samples for pharmacokinetic assessment will be drawn at specified timepoints and glucose infusion rates and blood glucose concentrations will be recorded for pharmacodynamic assessment during the 10-hour clamp procedure after dosing.

Official Title
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A Euglycaemic Clamp Trial to Evaluate the Pharmacokinetic and Pharmacodynamic Properties of a Bolus Dose of BioChaperone® Insulin Lispro, Fiasp® and NovoRapid® by an Insulin Pump

Conditions
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Type1 Diabetes Mellitus

Intervention / Treatment
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* Drug: BioChaperone® insulin lispro
* Drug: Fiasp®
* Drug: Novorapid®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 Diabetes Mellitus for more than 12 months. BMI between 18.5 and 28.5 kg/m². HbA1C level <=9.0%. Insulin treated for at least 12 months with total insulin dose <1.2U/kg/day. Exclusion Criteria: Type 2 Diabetes Mellitus. History of multiple and/or severe allergies to drugs or foods. Any history or presence of clinically relevant cardiovascular, pulmonary, respiratory, gastrointestinal, hepatic, renal, metabolic, endocrinological (with the exception of conditions associated with diabetes mellitus), haematological, dermatological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynaecologic (if female), or infectious disease, or signs of acute illness as judged by the Investigator. More than one episode of severe hypoglycaemia with seizure, coma or requiring assistance of another person during the past 6 months. Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy. Females of childbearing potential, who are pregnant, breast-feeding or intend to become pregnant or are not using highly effective contraceptive methods.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BioChaperone® insulin lispro<br>Single subcutaneous administration of BioChaperone® insulin lispro | Drug: BioChaperone® insulin lispro<br>* Single subcutaneous administration of a bolus of 0.15 U/kg body with a pump<br>|
| Active Comparator: Fiasp®<br>Single subcutaneous administration of Fiasp® (insulin aspart) | Drug: Fiasp®<br>* Single subcutaneous administration of a bolus of 0.15 U/kg body with a pump<br>|
| Active Comparator: Novorapid®<br>Single subcutaneous administration of Novorapid® (insulin aspart) | Drug: Novorapid®<br>* Single subcutaneous administration of a bolus of 0.15 U/kg body with a pump<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCGIR(0-60min) | Baseline corrected area under the glucose infusion rate curve from 0 to 60 minutes after bolus administration | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCins(0-30min) | Baseline corrected area under the insulin concentration time curve from 0 to 30 minutes after bolus administration | 30 minutes | 
| AUCins(0-60min) | Baseline corrected area under the insulin concentration time curve from 0 to 60 minutes after bolus administration | 60 minutes | 
| AUCins(0-600min) | Baseline corrected area under the insulin concentration time curve from 0 to 600 minutes after bolus administration | 600 minutes | 
| Cmax insulin | Maximum observed baseline corrected insulin concentration | 10 hours | 
| Tmax insulin | Time from bolus administration to baseline corrected Cmax | 10 hours | 
| TmaxGIR | Time from bolus administration to maximum baseline corrected glucose infusion rate | 10 hours | 
| GIRmax | Maximum baseline corrected glucose infusion rate | 10 hours | 
| Adverse Events | Number of Adverse Events in each arm | up to 8 weeks | 
| Clinical safety laboratory | Haematology, biochemistry and urinalysis: changes and findings from Baseline in clinical safety laboratory parameters during the trial duration, from screening, and at follow-up visit. | up to 8 weeks |