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| Name | Class |
|---|---|
| Tonghua Dongbao Pharmaceutical Co.,Ltd | INDUSTRY |
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This is a randomised, double-blind, double-dummy, active-controlled, three-period crossover euglycemic clamp trial in healthy Chinese volunteers.
Each subject will be randomly allocated to one of 6 treatment sequences. Each sequence comprises one single dose of BC Combo THDB0207, one single dose of Humalog® Mix25, or simultaneous administration of Humalog® and Lantus®.
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.
Subjects will attend the study site in the morning in a fasted state and will be connected to an automated glucose clamp device (ClampArt). Prior to dose administration plasma glucose will be stabilised at a defined target level by means of an intravenous infusion of glucose or insulin. IMP administration will be done by an unblinded person by means of subcutaneous injections in the abdominal wall.
Following each dosing a euglycaemic glucose clamp procedure will be carried out for up to 30 hours.
The pharmacodynamic assessment will be based on the time course of glucose infusion rate (GIR) and plasma glucose.
Plasma insulin concentrations will be measured using a specific validated bioanalytical method differentiating concentrations of insulin glargine, of its main metabolites insulin-glargine-M1 and insulin-glargine M2, and of insulin lispro. Pharmacokinetic insulin assessments will be based on total insulin concentration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BC Combo THDB0207 | Experimental | Single administration of BC Combo THDB0207 |
|
| Humalog® Mix25 | Active Comparator | Single administration of Humalog® Mix25 |
|
| Humalog® and Lantus® | Active Comparator | Simultaneous administration of Humalog® and Lantus® |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Euglycemic clamp with BC Combo THDB0207 | Drug | Administration of a single dose of BC Combo THDB0207 during an euglycemic clamp procedure |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUCGIR 0-2h | Area under the glucose infusion rate curve until 2 hours after IMP dosing | From t=0 to t=2 hours after IMP administration |
| Measure | Description | Time Frame |
|---|---|---|
| AUCGIR 0-last | Area under the glucose infusion rate curve from 0 hours until the end of clamp | From t=0 to t= 30 hours after IMP administration |
| GIRmax | Maximum Glucose Infusion Rate |
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Inclusion Criteria:
Exclusion Criteria:
Women of childbearing potential who are not using a highly effective contraceptive method.
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| Name | Affiliation | Role |
|---|---|---|
| Oliver Klein, MD | Profil Institut für Stoffwechselforschung GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil Institut für Stoffwechselforschung GmbH | Neuss | 41460 | Germany |
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Three-period crossover
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| Euglycemic clamp with Humalog® Mix25 | Drug | Administration of a single dose of Humalog® Mix25 during an euglycemic clamp procedure |
|
| Euglycemic clamp with Humalog® and Lantus® | Drug | Simultaneous administration of Humalog® and Lantus® during an euglycemic clamp procedure |
|
| From t=0 to t= 30 hours after IMP administration |
| AUCGIR 0-1h | Area under the glucose infusion rate curve until 1 hour after IMP dosing | From t=0 to t=1 hours after IMP administration |
| AUCGIR 0-6h | Area under the glucose infusion rate curve until 6 hours after IMP dosing | From t=0 to t=6 hours after IMP administration |
| AUCGIR 0-24h | Area under the glucose infusion rate curve until 24 hours after IMP dosing | From t=0 to t=24 hours after IMP administration |
| tGIRmax | Time to maximum glucose infusion rate | From t=0 to t=30 hours after IMP administration |
| tonset of action | Time until plasma glucose (PG) has decreased by at least 5 mg/dL from the baseline PG value | From t=0 to t=30 hours after IMP administration |
| AUCINSlast | Area under the insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ | From t=0 to t=30 hours after IMP administration |
| AUCINS 0-2h | Area under the insulin concentration-time curve during from t=0 to t=2h | From t=0 to t=2 hours after IMP administration |
| AUCINS 0-6h | Area under the insulin concentration-time curve during from t=0 to t=6h | From t=0 to t=6 hours after IMP administration |
| AUCINS 2-4h | Area under the insulin concentration-time curve during from t=2 to t=4h | From t=2 to t=4 hours after IMP administration |
| AUCINS 6-12h | Area under the insulin concentration-time curve during from t=6 to t=12h | From t=6 to t=12 hours after IMP administration |
| AUCINS 12-30h | Area under the insulin concentration-time curve during from t=12 to t=30h | From t=12 to t=30 hours after IMP administration |
| AUCINS 0-30h | Area under the insulin concentration-time curve during from t=0 to t=30h | From t=0 to t=30 hours after IMP administration |
| CmaxINS | Maximum insulin concentration | From t=0 to t= 30 hours after IMP administration |
| Tonset ins | Tonset of insulin appearance | From t=0 to t=30 hours |
| Adverse Events | Incidence of adverse events | From the first IMP administration to the follow-up visit (i.e. up to 11 weeks) |
| Serious Adverse Events | Incidence of Serious Adverse Events | From the first IMP administration to the follow-up visit (i.e. up to 11 weeks) |
| Local tolerability | Incidence of injection site reactions | From the first IMP administration to the follow-up visit (i.e. up to 11 weeks) |
| ID | Term |
|---|---|
| D015309 | Glucose Clamp Technique |
| D061268 | Insulin Lispro |
| D000069036 | Insulin Glargine |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| 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 |
| D049528 | Insulin, Long-Acting |
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