A Trial to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a double-blind, randomised, controlled, two-period crossover phase Ib trial using an individualised standard meal with a fixed nutrient ratio in subjects with type 2 diabetes mellitus to investigate post-prandial blood glucose control with BioChaperone insulin lispro compared to insulin lispro (Humalog®, Eli Lilly and Company) before and after a period of multiple daily dose administrations for 14 days. Each subject will be randomised to a sequence of two treatments, either BioChaperone insulin lispro-Humalog® or Humalog®-BioChaperone insulin lispro. Injections will take place immediately before an individualised standard meal in the morning of day 1, 2, 13, and 14. Insulin doses will be determined at the screening visit. During the outpatient phase the subjects will keep their basal insulin constant (except changes for safety reason). They will self-measure blood glucose at least 4 times daily (pre-prandial and at bedtime). In addition, on two days per outpatient period (Day 5 and 9) blood glucose will be measured 7 times daily (pre-prandial, 2 hours post-prandial and at bedtime).

Official Title
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A Randomised, Monocentric, Double-blind, Multiple Daily Dose, Two-period 14 Day Cross-over Trial to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of Individualised Doses of BioChaperone Insulin Lispro in Comparison to Humalog® U-100 in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: BioChaperone insulin lispro
* Drug: Humalog®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus ≥ 12 months Treated with stable multiple daily insulin ≥ 3 months (basal-bolus therapy or only bolus insulin therapy) Current total daily insulin treatment <1.2 (I)U/kg/day Body Mass Index below or equal to 40.0 kg/m² HbA1c ≤ 9.0% by local laboratory analysis Exclusion Criteria: Known or suspected hypersensitivity to trial products or related products Type 1 diabetes mellitus Previous participation in this trial The receipt of any investigational product within 60 days 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 Presence of renal impairment (Estimated Glomerular filtration Rate (eGFR)<60 milliliters/minute/1.73m²) Presence of late diabetic complications and/or acute coronary heart disease. 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 Current treatment with corticosteroids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 insulin lispro<br> | Drug: BioChaperone insulin lispro<br>* Injection immediately before the start of the individualised standard meal<br>|
| Active Comparator: Humalog®<br> | Drug: Humalog®<br>* Injection immediately before the start of the individualised standard meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics: ΔAUCBG 0-2h | Incremental Area Under Blood Glucose concentration-time Curve from 0-2 hours after a meal (comparison between BioChaperone insulin lispro and insulin lispro) | 2 hours | 
| Pharmacokinetics: AUClis 0-30min | Area Under the serum insulin Lispro concentration-time Curve 0-30 minutes (comparison between BioChaperone insulin lispro and insulin lispro) | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClisp_0-6h | Area Under the serum insulin Lispro concentration-time Curve from 0-6 hours after bolus dose | up to 6 hours | 
| Cmax_lisp | Maximum serum insulin lispro Concentration | up to 6 hours | 
| tmax_lisp | Time to maximum observed serum insulin lispro concentration | up to 6 hours | 
| CmaxBG | Maximum Blood Glucose after an individualised standard meal | up to 6 hours | 
| AUCBG_0-6h | Area Under the Curve under the Blood Glucose concentration time curve from 0-6 hours | up to 6 hours | 
| Adverse Events | Number of Adverse Events | up to 8 weeks | 
| Local tolerability | Record of injection site reaction | up to 8 weeks |