To Investigate the Efficacy and Safety of Individualized Doses of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a double-blind, randomised, controlled, two period crossover phase Ib trial using an individualized standard meal with a fixed nutrient ratio in subjects with type 1 diabetes mellitus to investigate postprandial blood glucose control with BioChaperone insulin lispro compared to Humalog®. The assessments will be conducted before and after a period of multiple daily dose administrations for 14 days. The meal tolerance test will be performed on day 1-3 and on day 14 of each period. Furthermore the study aims at investigating Post-prandial glucose (PPG) profiles with BioChaperone insulin lispro and Humalog® when injected at various injection meal intervals (-15min, 0 minutes, +15 minutes). Each subject will be randomised to a sequence of two treatments, either BioChaperone insulin lispro-Humalog® or Humalog®-Biochaperone insulin lispro, and three different sequences of injection-meal intervals. A blinded to patient continuous monitoring of glucose (CGM) will be performed during the 14 day treatment periods.

Official Title
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A Randomized, Monocentric, Double-blind, Multiple Daily Dose, Two-period, 14 Day Cross-over Trial to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of Individualized Doses of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 1 Diabetes Mellitus

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 mellitus (as diagnosed clinically) ≥ 12 months Treated with multiple daily insulin injections (no pump users) ≥ 12 months Current total daily insulin treatment <1.2 (I)U/kg/day Body mass index (BMI) 18.5-28.0 kg/m² (both inclusive) HbA1c (N-(1-deoxy)-fructosyl-haemoglobin) ≤ 9.0% by local laboratory analysis Fasting C-peptide ≤ 0.30 nmol/L Exclusion Criteria: Known or suspected hypersensitivity to trial products or related products Type 2 diabetes mellitus Patients using continuous subcutaneous insulin infusion (CSII) Previous participation in this trial. Participation is defined as randomised The receipt of any investigational product within 3 months prior to this trial Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis screening tests, as judged by the Investigator considering the underlying disease Presence of clinically significant acute gastrointestinal symptoms (e.g. nausea, vomiting, heartburn or diarrhoea), as judged by the Investigator Known slowing of gastric emptying and or gastrointestinal surgery that in the opinion of the investigator might change gastrointestinal motility and food absorption Unusual meal habits and special diet requirements or unwillingness to eat the food provided in the trial

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> | Drug: BioChaperone insulin lispro<br>* Injection at t0,or t+15 minutes or t-15minutes with test meal<br>|
| Active Comparator: Humalog®<br> | Drug: Humalog®<br>* Injection at t0,or t+15 minutes or t-15minutes with test meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCΔBG0-2h (timepoint 0 = administration of the meal) | Incremental area under the blood glucose (BG) concentration-time curve from 0-2 hours after a meal on day 1-3 [comparison between treatments Biochaperone insulin lispro vs. lispro (Humalog®)] | 2 hours | 
| AUClispro 0-30min (timepoint 0 = time of dosing) | Area under the serum insulin lispro concentration-time curve from 0-30 minutes after bolus dose on one of days 1, 2 or 3 (comparison between treatments BioChaperone insulin lispro vs. lispro (Humalog®)) | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClispro_0-6h | Area under the serum insulin lispro concentration-time curve from 0-6 hours after bolus dose | 6 Hours | 
| Cmax_lispro | Maximum serum insulin lispro concentration | up to 6 Hours | 
| Tmax_lispro | Time to maximum observed serum insulin lispro concentration | up to 6 Hours | 
| AUCBG_0-6h | Area under the curve under the blood glucose (BG) concentration time curve from 0-6 hours | 6 Hours | 
| ΔBGmax | Maximum blood glucose (BG) excursion after a standard meal (0-6 hours) | 6 Hours | 
| Adverse events | Number of Adverse events | Up to 3 months | 
| Local tolerability injection site reactions | Injection site reactions over 14 days of exposure | 14 days |