Postprandial Blood Glucose Control With BioChaperone® Combo and Insulin Lispro (Humalog®) Mix 25 in People With Type 1 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
Each subject will be randomly allocated to a sequence of two treatments applied at two separate dosing visits. At each dosing visit subjects will be injected with individualised doses of either BioChaperone® Combo or Humalog® Mix 25 immediately before ingesting a standardised mixed meal [(t=0 min) start of the meal]. Insulin doses will be identical at both dosing visits of one individual and will be administered subcutaneously in the abdominal region. Subjects will be asked to consume a standardised meal (e.g. pizza) for dinner at home in the evening before each dosing visit. Subjects will attend the clinical site in a fasted state in the morning of each dosing day and stay at the clinical trial centre until 10-hour after dosing (standardised test-meal procedure has been terminated after 6h). The two dosing visits will be separated by a wash-out period of 5-15 days.

Official Title
-----------------
Postprandial Blood Glucose Control With BioChaperone® Combo and Insulin Lispro (Humalog®) Mix 25 in People With Type 1 Diabetes Mellitus

Conditions
-----------------
Type 1 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Biochaperone® Combo
* Drug: Humalog® Mix25


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 1 diabetes mellitus (as diagnosed clinically) >= 12 months. Treated with multiple daily insulin injections or CSII >= 12 months. Current total daily insulin treatment < 1.2 (I)U/kg/day. Current total daily bolus insulin treatment < 0.7 (I)U/kg/day. Usual Insulin bolus dose between 0.8 and 2 (I)U per 10 g CH (both inclusive). Expecting prandial insulin dose range for standardised meal test between 5 and 12 (I)U. BMI 18.5-28.0 kg/m^2 (both inclusive). HbA1c <= 9.0% by local laboratory analysis Fasting C-peptide <= 0.3 nmol/L. Exclusion Criteria: Known or suspected hypersensitivity to trial products or related products. Type 2 diabetes mellitus. Previous participation in this trial. Participation is defined as randomised. Participation in any Clinical Trial 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. Women of child bearing potential, not willing to use contraceptive methods.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BioChaperone® Combo<br>1 single dose 400 U/mL | Drug: Biochaperone® Combo<br>* Subcutaneous injection of an individualized dose<br>|
| Active Comparator: Humalog® Mix25<br>1 single dose 100 U/mL | Drug: Humalog® Mix25<br>* Subcutaneous injection of an individualized dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta AUCBG,0-2h | Incremental area under the blood glucose concentration-time curve from 0-2 hours after a standardised meal | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta AUCBG,0-6h | Incremental area under the blood glucose concentration-time curve from 0-6 hours after a standardised meal | 6 hours | 
| BGmax | Maximum blood glucose concentration after a standardised meal (0-6 hours) | 6 hours | 
| tBGmax | Time to maximum blood glucose concentration after a standardised meal (0-6 hours) | 6 hours | 
| AUCLisp,0-6h, | Area under the plasma insulin lispro concentration-time curve from 0-6 hours | 6 hours | 
| AUCGlarg,0-6h | Area under the plasma insulin glargine concentration-time curve from 0-6 hours | 6 hours | 
| Cmax,Lisp | Maximum observed plasma insulin lispro concentration | 6 hours | 
| Cmax,Glarg | Maximum observed plasma insulin glargine concentration | 6 hours | 
| Adverse events | Number of adverse events | Up to 7 weeks | 
| Local tolerability | Number and intensity of injection site reactions | Up to 7 weeks |