A Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a single-centre, randomised, double-blind, 4-way crossover, 4-treatment, euglycaemic clamp study in subjects with Type 1 Diabetes Mellitus (T1DM). Each subject will be randomly allocated to one of four treatment sequences. Each sequence comprises one single dose of each of four IMPs. IMP1 and IMP2 are BioChaperone lispro formulations. They have the same composition and correspond to different development stages of a unique product which is BioChaperone insulin lispro; between them, improvements were made to prepare industrial production. Comparators (IMP3 and IMP4) are US-approved Humalog® and EU-approved Humalog®. All IMPs will be dosed at 0.2 U/Kg of insulin lispro on 4 dosing visits separated by a washout period of 5 to 15 days. The trial will compare the characteristics of BioChaperone insulin lispro fully liquid (IMP2) formulation to US-approved Humalog and EU-approved Humalog.

Official Title
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A Randomised, Double Blind, Crossover Euglycaemic Clamp Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)
* Drug: Administration of Ready-to-use BioChaperone insulin lispro (IMP2)
* Drug: Administration of US-approved Humalog® (IMP3)
* Drug: Administration of EU-approved Humalog® (IMP4)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with type 1 Diabetes Mellitus Body Mass Index (BMI) between 18.5 and 28.5 kg/m^2, both inclusive HbA1c <= 75 mmol/mol (<=9.0%). Fasting negative C-peptide (<= 0.30 nmol/L). Total insulin dose of < 1.2 (I)U/kg/day. Stable insulin regimen (with respect to safety of the subject and scientific integrity of the study) using continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI) for at least 2 months. Exclusion Criteria: Known or suspected hypersensitivity to IMP(s) or related products. Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomisation in this trial. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction. Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator. Any history or presence of clinically relevant comorbidity capable of constituting a risk for the subject when participating in the trial or of interfering with the interpretation of data. Signs of acute illness as judged by the Investigator. Any serious systemic infectious disease during four weeks prior to first dosing of the trial drug, as judged by the Investigator. Clinically significant abnormal screening laboratory tests, as judged by the Investigator. Proliferative retinopathy or maculopathy as judged by the Investigator based on a recent (<1.5 years) ophthalmologic examination. Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists 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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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 reconstituted with Humalog® (IMP1)<br>Subcutaneous administration of Biochaperone insulin lispro formulation made from a freeze-dried of BioChaperone reconstituted with Humalog® at a dose of 0.2 U/Kg Body Weight (BW). | Drug: Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)<br>* Administration of IMP1 during a 12-hour euglycaemic clamp.<br>|
| Experimental: Ready-to-use BioChaperone insulin lispro (IMP2)<br>Subcutaneous administration of ready-to-use Biochaperone insulin lispro formulation at a dose of 0.2 U/Kg BW. | Drug: Administration of Ready-to-use BioChaperone insulin lispro (IMP2)<br>* Administration of IMP2 during a 12-hour euglycaemic clamp.<br>|
| Active Comparator: US-approved Humalog® (IMP3)<br>Subcutaneous administration of US-approved Humalog® at a dose of 0.2 U/Kg BW. | Drug: Administration of US-approved Humalog® (IMP3)<br>* Administration of IMP3 during a 12-hour euglycaemic clamp.<br>|
| Active Comparator: EU-approved Humalog® (IMP4)<br>Subcutaneous administration of EU-approved Humalog® at a dose of 0.2 U/Kg BW. | Drug: Administration of EU-approved Humalog® (IMP4)<br>* Administration of IMP4 during a 12-hour euglycaemic clamp.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCGIR.0-12h | Area under the glucose infusion rate-time curve from time 0 until end of clamp | From t=0 to t=12 hours after IMP administration | 
| AUCGIR.0-1h | Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration | From t=0 to t=1 hour after IMP administration | 
| AUCLIS.0-12h | Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration | From t=0 to t=12 hours after IMP administration | 
| AUCLIS.0-1h | Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration | From t=0 to t=1 hour after IMP administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tmax.LIS | Time to maximum observed insulin lispro concentration | From t=0 to t=12 hours after IMP administration | 
| Cmax.LIS | Maximum observed insulin lispro concentration | From t=0 to t=12 hours after IMP administration | 
| AUCLIS.2-6h | Area under the insulin lispro concentration-time curve from 2 hour to 6 hour after dose administration | From t=2 to t=6hours after IMP administration | 
| t50%-LIS (early) | Time to half-maximum before Cmax.LIS | From t=0 to t=12 hours after IMP administration | 
| tmax.GIR | Time to maximum glucose infusion rate | From t=0 to t=12 hours after IMP administration | 
| GIRmax | Maximum glucose infusion rate | From t=0 to t=12 hours after IMP administration | 
| AUCGIR.4-8h | Area under the glucose infusion rate-time curve from 4 to 8 hours after dose administration | From t=4 to t=8 hours after IMP administration |