Clinical trial NCT05373186: A Trial Investigating the Pharmacodynamics of BC Combo THDB0207 Compared With Humalog® Mix25 and Simultaneous Injections of Humalog® and Lantus® in Healthy Chinese Volunteers
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Adocia
Sponsor class: INDUSTRY
Collaborators: name: Tonghua Dongbao Pharmaceutical Co.,Ltd
First posted: 2022-05-13
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Three-period crossover
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AUCGIR 0-2h
timeFrame: From t=0 to t=2 hours after IMP administration
Secondary outcomes:
measure: AUCGIR 0-last
timeFrame: From t=0 to t= 30 hours after IMP administration
measure: GIRmax
timeFrame: From t=0 to t= 30 hours after IMP administration
measure: AUCGIR 0-1h
timeFrame: From t=0 to t=1 hours after IMP administration
measure: AUCGIR 0-6h
timeFrame: From t=0 to t=6 hours after IMP administration
measure: AUCGIR 0-24h
timeFrame: From t=0 to t=24 hours after IMP administration
measure: tGIRmax
timeFrame: From t=0 to t=30 hours after IMP administration
measure: tonset of action
timeFrame: From t=0 to t=30 hours after IMP administration
measure: AUCINSlast
timeFrame: From t=0 to t=30 hours after IMP administration
measure: AUCINS 0-2h
timeFrame: From t=0 to t=2 hours after IMP administration
measure: AUCINS 0-6h
timeFrame: From t=0 to t=6 hours after IMP administration
measure: AUCINS 2-4h
timeFrame: From t=2 to t=4 hours after IMP administration
measure: AUCINS 6-12h
timeFrame: From t=6 to t=12 hours after IMP administration
measure: AUCINS 12-30h
timeFrame: From t=12 to t=30 hours after IMP administration
measure: AUCINS 0-30h
timeFrame: From t=0 to t=30 hours after IMP administration
measure: CmaxINS
timeFrame: From t=0 to t= 30 hours after IMP administration
measure: Tonset ins
timeFrame: From t=0 to t=30 hours
measure: Adverse Events
timeFrame: From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)
measure: Serious Adverse Events
timeFrame: From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)
measure: Local tolerability
timeFrame: From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH
name: Oliver Klein, MD
role: PRINCIPAL_INVESTIGATOR
References: