A Trial Investigating the Continuous Subcutaneous Insulin Infusion of a Liquid Formulation of BioChaperone Insulin Lispro in Comparison to Humalog®

Study Overview
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Brief Summary
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This study is constituted of 2 parts: Part A: A total of 36 patients will be enrolled in part A. Each eligible subject will participate in two 14-day treatment periods with Continuous Subcutaneous Insulin Infusion (CSII) of BioChaperone insulin lispro and insulin lispro (Humalog®, Eli Lilly and Company). Each treatment period consists of 10 treatment days under free living conditions (e.g. home / workplace) and under standardised conditions at the clinic. Various assessments for pharmacodynamics, pharmacokinetics, pump compatibility, short-term efficacy and safety are performed on selected days, including: Mixed Meal Test (MMT), Day 1, Day 3, Day 12 and Day 14, that will assess the post-prandial glucose response for 6 hours after individualized standard meal (fixed nutrient ratio) ingestion and bolus administration via CSII. Continuous Glucose Monitoring (CGM), (Day 1 - 14) that will be used in blinded mode (i.e. neither subjects nor the investigators are aware of the sensor glucose values). Pump compatibility (Day 1 - 14): Subjects will continue CSII treatment with the Investigational Medicinal Products (IMP) during the outpatient periods. Part B: A total of 44 patients will be enrolled. Subjects will be randomized to a 4-period cross-over study aiming at comparing the performance of BC Lispro and Humalog after a prandial bolus administration with two different CSII systems (Roche Accu-Chek® Spirit and Medtronic Paradigm® Veo™) or with a syringe. Pharmacodynamics, pharmacokinetics, pump compatibility and safety will be analyzed. Each period will include a mixed meal tolerance test with a CSII device and a mixed meal tolerance test with the same dose of insulin administered with a syringe.

Official Title
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A Trial Investigating the Continuous Subcutaneous Insulin Infusion of a Liquid Formulation of BioChaperone Insulin Lispro in Comparison to Humalog®

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: BioChaperone insulin lispro
* Drug: Humalog®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes for at least 12 months Body Mass Index (BMI) between 18.5 and 28.5 kg/m^2, both inclusive Using or having used a Roche CSII system (Accu-Chek® Spirit Combo/ Accu- Chek® Spirit) for at least 6 months before screening. In Part B subjects using any form of CSII treatment for at least 6 months before screening will be included. HbA1c <= 9.0%. Total insulin dose of < 1.2 (I)U/kg/day Ability to calculate insulin bolus manually or using a bolus calculator and willingness to consume regular meals, perform carbohydrate counting, self-monitoring of plasma glucose (SMPG) profiles and use of Continuous Glucose Monitoring (CGM). Fasting C-peptide <= 0.30 nmol/L Exclusion Criteria: Known or suspected hypersensitivity to Investigational Medicinal Product(s) (IMP(s)) or related products Type 2 diabetes mellitus Previous participation in this trial. Receipt of any investigational product in a clinical trial within 60 days before randomisation in this trial Clinically significant abnormal haematology, biochemistry, urinalysis, or coagulation screening test Presence of clinically significant acute gastrointestinal symptoms Known slowing of gastric emptying and or gastrointestinal surgery Unusual meal habits and special dietary requirements or unwillingness to eat the food provided in the trial History of diabetic ketoacidosis (DKA) episodes requiring hospitalization within 6 months prior to screening History of abscess at the infusion site within 6 months prior to screening Hypoglycaemia unawareness as judged by the Investigator History of severe hypoglycaemic episodes requiring hospitalization within the last 6 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BioChaperone insulin lispro<br> | Drug: BioChaperone insulin lispro<br>* BioChaperone insulin lispro bolus infusion followed by test meal intake<br>|
| Active Comparator: Humalog®<br>Insulin lispro | Drug: Humalog®<br>* Humalog® bolus infusion followed by test meal intake<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics: ΔAUCBG 0-2h | Incremental Area Under the Blood Glucose concentration-time Curve from 0-2 hours after the start of the meal. | 2 Hours | 
| Pharmacokinetics: AUClis 0-30min | Area Under the serum insulin Lispro concentration-time Curve from 0-30 minutes | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClis_0-6h | Area Under the baseline adjusted insulin Lispro Curve from 0-6h following a bolus dose | up to 6 Hours | 
| Cmax | Maximum insulin Concentration following a bolus dose | up to 6 Hours | 
| tCmax | Time to Maximum insulin Concentration following a bolus dose | up to 6 Hours | 
| BGmax | Maximum Blood Glucose after start of an individualised standardised meal intake | up to 6 Hours | 
| tBGmax | Time to Maximum Blood Glucose concentration | up to 6 Hours | 
| Compatibility | Number of suspected episodes of infusion set occlusion or leakage | up to 14 days | 
| Adverse Events | Number of Adverse Events | up to 12 weeks | 
| Local tolerability | Number of injection site reactions | up to 12 weeks |