A Trial Investigating the Pharmacodynamics of BC Combo THDB0207 Compared With Humalog® Mix25 and Simultaneous Injections of Humalog® and Lantus® in Healthy Chinese Volunteers

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Trial Investigating the Pharmacodynamics of BC Combo THDB0207 Compared With Humalog® Mix25 and Simultaneous Injections of Humalog® and Lantus® in Healthy Chinese Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Euglycemic clamp with BC Combo THDB0207
* Drug: Euglycemic clamp with Humalog® Mix25
* Drug: Euglycemic clamp with Humalog® and Lantus®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Chinese origin. To qualify as a subject of Chinese origin (first-generation Chinese), the subject, the subject's biological parents, and all of the subject's biological grandparents are of exclusive Chinese descent and have been born in China. BMI between 18.5 and 30.0 kg/m2, both inclusive. Fasting plasma glucose concentration <= 5.6 mmol/L (100 mg/dL). Exclusion Criteria: Known or suspected hypersensitivity to IMP(s) or any of the excipients or to any component of the IMP formulation. Receipt of any investigational medicinal product within 3 months before randomisation in this trial. Women of childbearing potential who are not using a highly effective contraceptive method. Any history or presence of a life-threatening disease (i.e. cancer except basal cell skin cancer or squamous cell skin cancer), or of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic (including type 1 and type 2 diabetes mellitus, haematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynaecologic (if female), or infectious disease, or signs of acute illness as judged by the investigator. Heart rate at rest outside the range of 50-90 beats per minute. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Three-period crossover
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BC Combo THDB0207<br>Single administration of BC Combo THDB0207 | Drug: Euglycemic clamp with BC Combo THDB0207<br>* Administration of a single dose of BC Combo THDB0207 during an euglycemic clamp procedure<br>|
| Active Comparator: Humalog® Mix25<br>Single administration of Humalog® Mix25 | Drug: Euglycemic clamp with Humalog® Mix25<br>* Administration of a single dose of Humalog® Mix25 during an euglycemic clamp procedure<br>|
| Active Comparator: Humalog® and Lantus®<br>Simultaneous administration of Humalog® and Lantus® | Drug: Euglycemic clamp with Humalog® and Lantus®<br>* Simultaneous administration of Humalog® and Lantus® during an euglycemic clamp procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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) |