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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Euglycemic clamp with BC Combo THDB0207; Drug: Euglycemic clamp with Humalog® Mix25; Drug: Euglycemic clamp with Humalog® and Lantus®

• Registration Number: NCT05373186
• Lead Sponsor: Adocia

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-05-04
• Study First Submitted QC: 2022-05-09
• Study Start: 2022-05-12
• Study First Posted: 2022-05-13
• Primary Completion: 2022-12-04
• Study Completion: 2022-12-04
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-10
• Last Update Posted: 2023-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BC Combo THDB0207	Euglycemic clamp with BC Combo THDB0207	Single administration of BC Combo THDB0207
Humalog® Mix25	Euglycemic clamp with Humalog® Mix25	Single administration of Humalog® Mix25
Humalog® and Lantus®	Euglycemic clamp with Humalog® and Lantus®	Simultaneous administration of Humalog® and Lantus®

Primary Outcome Measures

Name	Time	Method
AUCGIR 0-2h	From t=0 to t=2 hours after IMP administration	Area under the glucose infusion rate curve until 2 hours after IMP dosing

Secondary Outcome Measures

Name	Time	Method
AUCGIR 0-last	From t=0 to t= 30 hours after IMP administration	Area under the glucose infusion rate curve from 0 hours until the end of clamp
GIRmax	From t=0 to t= 30 hours after IMP administration	Maximum Glucose Infusion Rate
AUCGIR 0-1h	From t=0 to t=1 hours after IMP administration	Area under the glucose infusion rate curve until 1 hour after IMP dosing
AUCGIR 0-6h	From t=0 to t=6 hours after IMP administration	Area under the glucose infusion rate curve until 6 hours after IMP dosing
AUCGIR 0-24h	From t=0 to t=24 hours after IMP administration	Area under the glucose infusion rate curve until 24 hours after IMP dosing
tGIRmax	From t=0 to t=30 hours after IMP administration	Time to maximum glucose infusion rate
tonset of action	From t=0 to t=30 hours after IMP administration	Time until plasma glucose (PG) has decreased by at least 5 mg/dL from the baseline PG value
Adverse Events	From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)	Incidence of adverse events
Serious Adverse Events	From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)	Incidence of Serious Adverse Events
Local tolerability	From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)	Incidence of injection site reactions
Tonset ins	From t=0 to t=30 hours	Tonset of insulin appearance
AUCINSlast	From t=0 to t=30 hours after IMP administration	Area under the insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
AUCINS 0-2h	From t=0 to t=2 hours after IMP administration	Area under the insulin concentration-time curve during from t=0 to t=2h
AUCINS 0-6h	From t=0 to t=6 hours after IMP administration	Area under the insulin concentration-time curve during from t=0 to t=6h
AUCINS 2-4h	From t=2 to t=4 hours after IMP administration	Area under the insulin concentration-time curve during from t=2 to t=4h
AUCINS 6-12h	From t=6 to t=12 hours after IMP administration	Area under the insulin concentration-time curve during from t=6 to t=12h
AUCINS 12-30h	From t=12 to t=30 hours after IMP administration	Area under the insulin concentration-time curve during from t=12 to t=30h
AUCINS 0-30h	From t=0 to t=30 hours after IMP administration	Area under the insulin concentration-time curve during from t=0 to t=30h
CmaxINS	From t=0 to t= 30 hours after IMP administration	Maximum insulin concentration

Trial Locations

Locations (1)

Profil Institut für Stoffwechselforschung GmbH; 🇩🇪 Neuss, Germany