A Trial to Investigate the Dose-linearity of BioChaperone® Combo 75/25 and the Safety at Three Different Doses in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This is a bicentric, double-blinded, randomised, four-period crossover phase 1 trial, using automated 30-hour euglycemic clamp in subjects with type 2 diabetes mellitus.

Detailed Description
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This is a bicentric, double-blinded, randomised, four-period crossover phase 1 trial, using automated 30-hour euglycemic clamp in subjects with type 2 diabetes mellitus. Each subject will be randomly allocated to a sequence of four treatments, three single doses of BioChaperone® Combo 75/25 (0.6 U/kg, 0.8 U/kg or 1.0 U/kg) and one single dose of Humalog® Mix25 at 0.8 U/kg on four separate dosing visits. Subjects will come in a fasted state to the clinical trial centre in the morning of each dosing day and stay at the clinical trial centre until the 30-hour clamp procedures have been terminated.

Official Title
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A Double-blinded, Randomised, Four-period Crossover Euglycemic Clamp Trial Investigating the Dose-linearity of BioChaperone® Combo 75/25 and the Safety at Three Different Doses in Subjects With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: BioChaperone® Combo 75/25 at 0.6 U/kg
* Drug: BioChaperone® Combo 75/25 at 0.8 U/kg
* Drug: BioChaperone® Combo 75/25 at 1.0 U/kg
* Drug: Humalog® Mix25 at 0.8 U/kg


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 6.5% and 9.0 % (both inclusive) Body mass index between 20.0 and 40.0 kg/m2 (both inclusive) Body weight <= 125.0 kg at the screening visit Insulin-treated subjects. Total insulin dose of <= 1.2 (I)U/kg/day Exclusion Criteria: Type 1 diabetes mellitus Known or suspected hypersensitivity to IMP(s) or related products Previous participation in this trial. Participation is defined as randomised. Receipt of any medicinal product in clinical development within 60 days before randomisation in this trial. Clinically significant abnormal values for haematology, biochemistry, coagulation, or urinalysis as judged by the Investigator considering the underlying disease. Supine blood pressure at screening (after resting for at least 5 min in supine position) outside the range of 90-160 mmHg systolically or 50-95 mmHg diastolically (excluding white-coat hypertension; therefore, if a repeated measurement shows values within the range, the subject can be included in the trial); symptoms of arterial hypotension and/or a heart rate at rest outside the range of 50-90 beats per minute. This exclusion criterion also pertains to subjects being on anti-hypertensives. 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 75/25 at 0.6 U/kg<br>Single subcutaneous injection of 0.6 U/kg | Drug: BioChaperone® Combo 75/25 at 0.6 U/kg<br>* Injection of BioChaperone® Combo 75/25 at 0.6 U/kg<br>|
| Experimental: BioChaperone® Combo 75/25 at 0.8 U/kg<br>Single subcutaneous dose of 0.8 U/kg | Drug: BioChaperone® Combo 75/25 at 0.8 U/kg<br>* Injection of BioChaperone® Combo 75/25 at 0.8 U/kg<br>|
| Experimental: BioChaperone® Combo 75/25 at 1.0 U/kg<br>Single subcutaneous dose of 1.0 U/kg | Drug: BioChaperone® Combo 75/25 at 1.0 U/kg<br>* Injection of BioChaperone® Combo 75/25 at 1.0 U/kg<br>|
| Active Comparator: Humalog® Mix25 at 0.8 U/kg<br>Single subcutaneous dose of 0.8 U/kg | Drug: Humalog® Mix25 at 0.8 U/kg<br>* Injection of Humalog® Mix25 at 0.8 U/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC last_total | Area under the plasma insulin concentration-time curve from t=0 to the last measured total insulin plasma concentration above LLOQ. The total insulin concentration is the sum of lispro and basal concentrations. | From 0 to 30 hours | 
| Cmax_total | Maximum observed plasma insulin total concentration | From 0 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 | From 0 to 30 hours | 
| GIRmax (mg/kg/min) | Maximum glucose infusion rate | From 0 to 30 hours | 
| tGIRmax | Time to maximum glucose infusion rate | From 0 to 30 hours | 
| Adverse Events |  | Up to 102 days (maximum duration of subject's participation) | 
| Local tolerability: number of injection site reaction | Frequency of injection site reaction in each arm. | Up to 102 days (maximum duration of subject's participation) | 
| Number of hypoglycaemic events in each treatment arm |  | Up to 102 days (maximum duration of subject's participation) |