A Trial to Investigate Post Prandial Blood Glucose Control With Fast-acting Human Insulin HinsBet® Compared to Insulin Lispro (Humalog®) and Regular Human Insulin (Huminsulin® Normal) After Ingestion of a Standardized Meal in Subjects With T1DM

Study Overview
=================
Brief Summary
-----------------
This is a 2 centres, randomised, double blind, three-treatment, three-period cross-over trial in subjects with type 1 diabetes mellitus. Each subject will be administered individualised single subcutaneous doses of BioChaperone Human Insulin (HinsBet®), insulin lispro (Humalog®) and regular human insulin (Huminsulin® Normal) immediately before ingesting a standardised mixed meal. Following trial drug administration, PK and PD assessments will be carried until 6 hours after start of the standardized test meal. The total trial duration for an individual subject will be up to 11 weeks.

Official Title
-----------------
A Randomised, Double Blind, Three-period Cross-over Trial to Investigate Post Prandial Blood Glucose Control With Fast-acting Human Insulin HinsBet® Compared to Insulin Lispro (Humalog®) and Regular Human Insulin (Huminsulin® Normal) After Ingestion of a Standardized Meal in Subjects With Type 1 Diabetes Mellitus (T1DM)

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

Intervention / Treatment
-----------------
* Drug: BioChaperone Human Insulin (HinsBet®)
* Drug: Insulin Lispro (Humalog®)
* Drug: Regular human insulin (Huminsulin® Normal)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subject aged 18-64 years (both inclusive). 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. BMI 18.5-28.0 kg/m^2 (both inclusive). HbA1c <= 9.0 % by local laboratory analysis Fasting C-peptide <= 0.30 nmol/L. Exclusion Criteria: Known or suspected hypersensitivity to IMPs 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, coagulation, 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. 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
-----------------
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: HinsBet®<br> | Drug: BioChaperone Human Insulin (HinsBet®)<br>* BioChaperone Human Insulin (HinsBet®) individualised single subcutaneous injection followed by test meal intake<br>|
| Active Comparator: Humalog®<br> | Drug: Insulin Lispro (Humalog®)<br>* Insulin Lispro (Humalog®) individualised single subcutaneous injection followed by test meal intake<br>|
| Active Comparator: Huminsulin® Normal<br> | Drug: Regular human insulin (Huminsulin® Normal)<br>* Regular human insulin (Huminsulin® Normal) individualised single subcutaneous injection followed by test meal intake<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BG1h | Blood glucose (BG) concentration 1 hour after start of intake of a standardised meal | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ΔBG1h | Mean change from baseline of blood glucose concentration 1 hour after start of intake of a standardised meal | 1 hour | 
| AUCBG,0-1h | Area under the blood glucose concentration-time curve from 0-1 hour after a standardised meal | 1 hour | 
| ΔAUCBG,0-1h | Incremental area under the blood glucose concentration-time curve from 0-1 hour after a standardised meal | 1 hour | 
| AUCIns,0-1h | Area under the serum insulin concentration-time curve from 0-1 hour | 1 hour | 
| Adverse Events | Number of Adverse Events | Up to 11 weeks | 
| Local tolerability (Number of injection site reactions) | Number of injection site reactions | Up to 11 weeks |