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This is a single-centre, randomised, double-blind, 4-way crossover, 4-treatment, euglycaemic clamp study in subjects with Type 1 Diabetes Mellitus (T1DM). Each subject will be randomly allocated to one of four treatment sequences. Each sequence comprises one single dose of each of four IMPs. IMP1 and IMP2 are BioChaperone lispro formulations. They have the same composition and correspond to different development stages of a unique product which is BioChaperone insulin lispro; between them, improvements were made to prepare industrial production. Comparators (IMP3 and IMP4) are US-approved Humalog® and EU-approved Humalog®. All IMPs will be dosed at 0.2 U/Kg of insulin lispro on 4 dosing visits separated by a washout period of 5 to 15 days.
The trial will compare the characteristics of BioChaperone insulin lispro fully liquid (IMP2) formulation to US-approved Humalog and EU-approved Humalog.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BioChaperone insulin lispro reconstituted with Humalog® (IMP1) | Experimental | Subcutaneous administration of Biochaperone insulin lispro formulation made from a freeze-dried of BioChaperone reconstituted with Humalog® at a dose of 0.2 U/Kg Body Weight (BW). |
|
| Ready-to-use BioChaperone insulin lispro (IMP2) | Experimental | Subcutaneous administration of ready-to-use Biochaperone insulin lispro formulation at a dose of 0.2 U/Kg BW. |
|
| US-approved Humalog® (IMP3) | Active Comparator | Subcutaneous administration of US-approved Humalog® at a dose of 0.2 U/Kg BW. |
|
| EU-approved Humalog® (IMP4) | Active Comparator | Subcutaneous administration of EU-approved Humalog® at a dose of 0.2 U/Kg BW. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1) | Drug | Administration of IMP1 during a 12-hour euglycaemic clamp. |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUCGIR.0-12h | Area under the glucose infusion rate-time curve from time 0 until end of clamp | From t=0 to t=12 hours after IMP administration |
| AUCGIR.0-1h | Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration | From t=0 to t=1 hour after IMP administration |
| AUCLIS.0-12h | Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration | From t=0 to t=12 hours after IMP administration |
| AUCLIS.0-1h | Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration | From t=0 to t=1 hour after IMP administration |
| Measure | Description | Time Frame |
|---|---|---|
| tmax.LIS | Time to maximum observed insulin lispro concentration | From t=0 to t=12 hours after IMP administration |
| Cmax.LIS | Maximum observed insulin lispro concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eugen Baumgaertner, MD | Profil GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil GmbH | Mainz | D-55116 | Germany |
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| Administration of Ready-to-use BioChaperone insulin lispro (IMP2) | Drug | Administration of IMP2 during a 12-hour euglycaemic clamp. |
|
| Administration of US-approved Humalog® (IMP3) | Drug | Administration of IMP3 during a 12-hour euglycaemic clamp. |
|
| Administration of EU-approved Humalog® (IMP4) | Drug | Administration of IMP4 during a 12-hour euglycaemic clamp. |
|
| From t=0 to t=12 hours after IMP administration |
| AUCLIS.2-6h | Area under the insulin lispro concentration-time curve from 2 hour to 6 hour after dose administration | From t=2 to t=6hours after IMP administration |
| t50%-LIS (early) | Time to half-maximum before Cmax.LIS | From t=0 to t=12 hours after IMP administration |
| tmax.GIR | Time to maximum glucose infusion rate | From t=0 to t=12 hours after IMP administration |
| GIRmax | Maximum glucose infusion rate | From t=0 to t=12 hours after IMP administration |
| AUCGIR.4-8h | Area under the glucose infusion rate-time curve from 4 to 8 hours after dose administration | From t=4 to t=8 hours after IMP administration |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D061268 | Insulin Lispro |
| C460085 | signal peptide peptidase |
| C498779 | IGF2BP2 protein, human |
| ID | Term |
|---|---|
| D061266 | Insulin, Short-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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