A Trial to Compare the Pharmacodynamic and Pharmacokinetic Properties of Biochaperone® Combo With Humalog® Mix25 and With Simultaneous Injections of Humalog® and Lantus® in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This is a single centre, randomised, double-blind, double-dummy, 3-treatment, 3-period cross-over, euglycaemic clamp study in subjects with type 2 diabetes on stable insulin treatment. Each subject will be randomly allocated to a treatment sequence and will be administered single subcutaneous doses of 0.8 U/kg Biochaperone® Combo, 0.8 U/kg Humalog® Mix25 or simultaneous subcutaneous injections of 0.2 U/kg Humalog® and 0.6 U/kg Lantus® during three separate dosing visits.

Official Title
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A Randomised, Single Dose, Double-blind, Double-dummy, Three-period Cross-over Trial to Compare the Pharmacodynamic and Pharmacokinetic Properties of Biochaperone® Combo With Humalog® Mix25 and With Simultaneous Injections of Humalog® and Lantus® in Subjects With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Biochaperone Combo
* Drug: Humalog Mix25
* Drug: Humalog
* Drug: Lantus
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus (as diagnosed clinically) for ≥ 12 months HbA1c levels ≤ 9.0% Total insulin dose of < 1.2 U/kg/day Body mass index between 20.0 and 35.0 kg/m2 (both inclusive) Body weight ≤ 125.0 kg Fasting serum C-peptide ≤ 1 nmol/L Treated with a stable insulin regimen for ≥ 3 months prior to screening Exclusion Criteria: Type 1 diabetes mellitus Known or suspected allergy to the trial products or related products 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 Supine blood pressure at screening outside the range of 90-160 mmHg for systolic or 50-95 mmHg for diastolic and/or resting supine heart rate outside the range 50 -90 beats per minute. This exclusion criterion also pertains to subjects being on antihypertensives Use of GLP-1 receptor agonists or oral antidiabetic drugs (OADs) other than stable intake of metformin within 4 weeks prior to screening Women of child bearing potential, not willing to use contraceptive methods

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 Combo<br>single subcutaneous injection of 0.8 U/kg + injection of placebo (0.9% NaCl) to ensure the double dummy | Drug: Biochaperone Combo<br>* Injection of BioChaperone Combo<br>Drug: Placebo<br>* Injection of saline 0.9% solution<br>|
| Active Comparator: Humalog Mix25<br>single subcutaneous dose of 0.8 U/kg + injection of placebo (0.9% NaCl) to ensure the double dummy | Drug: Humalog Mix25<br>* Injection of Humalog Mix25<br>Drug: Placebo<br>* Injection of saline 0.9% solution<br>|
| Active Comparator: Humalog and Lantus<br>simultaneous subcutaneous injections of 0.2 U/kg Humalog and 0.6 U/kg Lantus | Drug: Humalog<br>* Injection of Humalog<br>Drug: Lantus<br>* Injection of Lantus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the glucose infusion rate curve (AUCGIR) 12-30h (mg/kg) | Area under the glucose infusion rate curve from 12 hours to 30 hours | from 12h to 30 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCGIR 0-last (mg/kg) | Area under the glucose infusion rate curve from 0 hours until the end of clamp | Up to 30 hours | 
| GIRmax (mg/kg/min) | Maximum glucose infusion rate | Up to 30 hours | 
| tGIRmax | Time to maximum glucose infusion rate | Up to 30 hours | 
| AUCLis 0-30h | Area under the insulin lispro plasma concentration time curve | Up to 30 hours | 
| AUCGla 0-30h | Area under the insulin glargine plasma concentration time curve | Up to 30 hours | 
| tmax Gla | Time to maximum insulin glargine plasma concentration | Up to 30 hours | 
| tmax Lis | Time to maximum insulin lispro plasma concentration | Up to 30 hours | 
| Adverse events | Number of adverse events | Up to 9 weeks | 
| Hypoglycaemic episodes | Number of Hypoglycaemic episodes | Up to 9 weeks | 
| Local tolerability | Number and intensity of injection site reactions | Up to 9 weeks |