A Trial to Compare Post Prandial Blood Glucose Control 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 two-centre, randomised, double-blind, double-dummy, 3-treatment, 3-period cross-over study using a standardised solid meal test in subjects with type 2 diabetes to investigate postprandial glucose control of BioChaperone® Combo compared with Humalog® Mix25 and with simultaneous subcutaneous injections of Humalog® and Lantus® during three separate dosing visits.

Detailed Description
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This is a two-centre, randomised, double-blind, double-dummy, 3-treatment, 3-period cross-over study using a standardised solid meal test in subjects with type 2 diabetes to investigate postprandial glucose control of BioChaperone® Combo compared with Humalog® Mix25 and with simultaneous subcutaneous injections of Humalog® and Lantus® during three separate dosing visits. Furthermore, this study aims to compare the pharmacokinetic (PK) profiles of the three different study treatments. During each dosing visit, subjects will be given 3 doses of IMP on three consecutive days (Day 1, Day 2 and Day 3). Dosing on Day 2 and Day 3 will be followed by a standardised solid meal test.

Official Title
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A Randomised, Double-blind, Double-dummy, Three-period Cross-over Trial to Compare Post Prandial Blood Glucose Control 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: Male or female subject aged 18-70 years (both inclusive) Type 2 diabetes mellitus (as diagnosed clinically) for ≥ 12 months HbA1c level between 7.5% and 9.5% (both inclusive) Body mass index between 20.0 and 40.0 kg/m2 (both inclusive) Treated with once daily injections with insulin glargine U-100 for ≥ 3 months prior to screening Exclusion Criteria: Type 1 diabetes mellitus Known or suspected allergy to the IMPs or related products Previous participation in this trial. Participation is defined as randomised. Receipt of any medicinal product in clinical development within 60 days prior to this trial. Clinically significant abnormal haematology, biochemistry, urinalysis or coagulation 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. Current treatment with premixed or intermediate insulin products, or with long acting insulins other than insulin glargine U-100. The use of short or rapid acting prandial insulin products will be allowed provided their use has been stable for ≥ 3 months prior to screening. Use of GLP-1 receptor agonists or oral antidiabetic drugs (OADs) other than stable intake of metformin alone or metformin in combination with a DPP-4 inhibitor 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: 70 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>Individualised single subcutaneous of BioChaperone® Combo + 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 0.9% NaCl<br>|
| Active Comparator: Humalog® Mix25<br>Individualised single subcutaneous of Humalog® Mix25 + 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 0.9% NaCl<br>|
| Active Comparator: Humalog® and Lantus®<br>Individualised simultaneous subcutaneous injections | 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 |
| --- | --- | --- |
| Delta AUC BG 0-2h (area under the blood glucose concentration-time curve) | Mean of incremental areas under the blood glucose concentration-time curve from 0-2 hours after a standardised meal on Day 2 and Day 3 | From 0 to 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial delta AUCs BG and total AUCs BG | Partial incremental AUCs BG and total AUCs BG in the 0-6 time range | From 0 to 6 hours | 
| Mean and mean change from baseline of blood glucose at different time points |  | From 0 to 6 hours | 
| Delta BGmax and delta BGmin | Maximum and minimum blood glucose excursions after a standardised meal | From 0 to 6 hours | 
| BGmax and BGmin | Maximum and minimum blood glucose concentrations after a standardised meal | From 0 to 6 hours | 
| AUC Insulin | Partial areas under the insulins plasma concentration time curve | From 0 to 24 hours | 
| Cmax Insulin | Maximum observed plasma insulins concentration | From 0 to 6 hours | 
| tmax Insulin | Time to maximum observed plasma insulins concentration | From 0 to 6 hours | 
| Adverse Events |  | Up to 12 weeks (maximum duration of subject's participation) | 
| Local tolerability |  | Up to 12 weeks (maximum duration of subject's participation) | 
| Hypoglycaemic events |  | Up to 12 weeks (maximum duration of subject's participation) |