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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Euglycemic clamp with BC Combo THDB0207; Drug: Euglycemic clamp with Humalog® Mix25; Drug: Euglycemic clamp with Humalog® and Lantus®

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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
Local tolerability	Incidence of injection site reactions	From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)
tGIRmax	Time to maximum glucose infusion rate	From t=0 to t=30 hours after IMP administration
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
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 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)
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

Collaborators and Investigators

• Sponsor: Adocia
• Collaborators: Tonghua Dongbao Pharmaceutical Co.,Ltd
• Investigators: Principal Investigator: Oliver Klein, MD, Profil Institut für Stoffwechselforschung GmbH

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Actual): December 4, 2022
• Study Completion (Actual): December 4, 2022

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: CT046-ADO05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No