A Trial Investigating the Dose Linearity and Safety of BC Combo THDB0207 in Subjects With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

Official title:

A Trial Investigating the Dose Linearity and Safety of BC Combo THDB0207 in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05373212
• Other study ID #: CT048-ADO05
• Status: Completed
• Phase: Phase 1
• Start date: May 12, 2022
• Est. completion date: January 2, 2023

Study information

• Verified date: September 2023
• Source: Adocia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomised, double-blind, four-period crossover euglycaemic clamp trial in subjects with type 2 diabetes. Each subject will be randomly allocated to one of four treatment sequences. Each sequence will comprise 3 different single doses of BC Combo THDB0207 (Low dose, Medium dose, and High dose) and one single dose of Humalog® Mix25. Subjects will come to the clinical trial centre in a fasted state in the morning of each dosing day and stay at the clinical trial centre until the 30-hour clamp procedures have been terminated.

Description:

Subjects will attend the study site in the morning in a fasted state and will be connected to an automated glucose clamp device. Prior to dose administration plasma glucose will be stabilised at a target level of 100 mg/dL 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 assessments will be based on total insulin concentration (insulin glargine + insulin glargine-M1 + insulin glargine-M2 + insulin lispro), on insulin glargine concentration (insulin glargine + insulin glargine-M1 + insulin glargine-M2), or on insulin lispro concentration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2, 2023
• Est. primary completion date: January 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes mellitus (as diagnosed clinically) for = 12 months
• HbA1c =9.0%
• Total insulin dose of < 1.2 U/kg/day
• Body mass index between 20.0 and 35.0 kg/m2 (both inclusive)
• Treated with a stable insulin regimen for = 3 months prior to screening

Exclusion Criteria:

• Known or suspected hypersensitivity to the IMPs or any of the excipients or to any component of the IMP formulation
• Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomisation in this trial
• Clinically significant abnormal screening laboratory tests, as judged by the Investigator considering the underlying disease
• Clinically relevant comorbidity, capable of constituting a risk for the subject when participating in the trial or of interfering with the interpretation of data
• Systolic blood pressure < 90 mmHg or >160 mmHg and/or diastolic blood pressure < 50 mmHg or > 95 mmHg (one repeat test will be acceptable in case of suspected white-coat hypertension)
• Heart rate at rest outside the range of 50-90 beats per minute
• Use of GLP-1 receptor agonists or oral antidiabetic drugs (OADs) other than stable intake of metformin within 4 weeks prior to screening
• Women of childbearing potential who are not using a highly effective contraceptive method

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Euglycemic clamp with BC Combo THDB0207
Administration of a single dose of BC Combo THDB0207 during an euglycemic clamp procedure.
• Euglycemic clamp with Humalog® Mix25
Administration of a single dose of Humalog® Mix25 during an euglycemic clamp procedure.

Locations

Country	Name	City	State
Germany	Profil Institut für Stoffwechselforschung GmbH	Neuss

Sponsors (2)

Lead Sponsor	Collaborator
Adocia	Tonghua Dongbao Pharmaceutical Co.,Ltd

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUCTOTAL0-last	Area under the total 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
Primary	CmaxTOTAL	Maximum total insulin concentration	From t=0 to t=30 hours after IMP administration
Secondary	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
Secondary	GIRmax	Maximum glucose infusion rate	From t=0 to t=30 hours after IMP administration
Secondary	tGIRmax	Time to maximum glucose infusion rate	From t=0 to t=30 hours after IMP administration
Secondary	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
Secondary	AUCGIR 0-6h	Area under the glucose infusion rate curve from t=0 hours to t=6 hours	From t=0 to t=6 hours
Secondary	AUCTOTALlast	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
Secondary	AUCTOTAL 0-1h	Area under the total insulin concentration-time curve from t=0 to t=1 hour	From t=0 to t=1 hour
Secondary	AUCTOTAL 0-2h	Area under the total insulin concentration-time curve from t=0 to t=2 hours	From t=0 to t=2 hours
Secondary	AUCTOTAL 0-6h	Area under the total insulin concentration-time curve from t=0 to t=6 hours	From t=0 to t=6 hours
Secondary	AUCTOTAL 2-6h	Area under the total insulin concentration-time curve from t=2 to t=6 hours	From t=2 to t=6 hours
Secondary	AUCTOTAL 6-12h	Area under the total insulin concentration-time curve from t=6 to t=12 hours	From t=6 to t=12 hours
Secondary	AUCTOTAL 6-24h	Area under the total insulin concentration-time curve from t=6 to t=24 hours	From t=6 to t=24 hours
Secondary	AUCTOTAL 12-24h	Area under the total insulin concentration-time curve from t=12 to t=24 hours	From t=12 to t=24 hours
Secondary	AUCTOTAL 12-30h	Area under the total insulin concentration-time curve from t=12 to t=30 hours	From t=12 to t=30 hours
Secondary	AUCTOTAL 0-30h	Area under the total insulin concentration-time curve from t=0 to t=30 hours	From t=0 to t=30 hours
Secondary	CTOTALmax	Maximum insulin concentration	From t=0 to t=30 hours after IMP administration
Secondary	tmaxTOTAL	Time to maximum total insulin concentration	From t=0 to t=30 hours after IMP administration
Secondary	AUCGLA 0-last	Area under the insulin glargine concentration-time curve from t=0 to the last measured insulin concentration above LLOQ	From t=0 to t=30 hours after IMP administration
Secondary	AUCGLA 0-1h	Area under the insulin glargine concentration-time curve from t=0 to t=1 hour	From t=0 to t=1 hour after IMP administration
Secondary	AUCGLA 0-2h	Area under the insulin glargine concentration-time curve from t=0 to t=2 hours	From t=0 to t=2 hours after IMP administration
Secondary	AUCGLA 0-6h	Area under the insulin glargine concentration-time curve from t=0 to t=6 hours	From t=0 to t=6 hours after IMP administration
Secondary	AUCGLA 2-6h	Area under the insulin glargine concentration-time curve from t=2 to t=6 hours	From t=2 to t=6 hours after IMP administration
Secondary	AUCGLA 6-12h	Area under the insulin glargine concentration-time curve from t=6 to t=12 hours	From t=6 to t=12 hours after IMP administration
Secondary	AUCGLA 12-24h	Area under the insulin glargine concentration-time curve from t=12 to t=24 hours	From t=12 to t=24 hours after IMP administration
Secondary	AUCGLA 12-30h	Area under the insulin glargine concentration-time curve from t=12 to t=30 hours	From t=12 to t=30 hours after IMP administration
Secondary	AUCGLA 0-30h	Area under the insulin glargine concentration-time curve from t=0 to t=30 hours	From t=0 to t=30 hours after IMP administration
Secondary	CmaxGLA	Maximum concentration of insulin glargine	From t=0 to t=30 hours after IMP administration
Secondary	tmaxGLA	Time to maximum insulin glargine concentration	From t=0 to t=30 hours after IMP administration
Secondary	AUCLIS0-last	Area under the insulin lispro concentration-time curve from t=0 to the last measured insulin concentration above LLOQ	From t=0 to t=30 hours after IMP administration
Secondary	AUCLIS 0-1h	Area under the insulin lispro concentration-time curve from t=0 to t=1 hour	From t=0 to t=1 hour after IMP administration
Secondary	AUCLIS 0-2h	Area under the insulin lispro concentration-time curve from t=0 to t=2 hours	From t=0 to t=2 hours after IMP administration
Secondary	AUCLIS 0-6h	Area under the insulin lispro concentration-time curve from t=0 to t=6 hours	From t=0 to t=6 hours after IMP administration
Secondary	AUCLIS 2-6h	Area under the insulin lispro concentration-time curve from t=2 to t=6 hours	From t=2 to t=6 hours after IMP administration
Secondary	AUCLIS 6-12h	Area under the insulin lispro concentration-time curve from t=6 to t=12 hours	From t=6 to t=12 hours after IMP administration
Secondary	AUCLIS 12-24h	Area under the insulin lispro concentration-time curve from t=12 to t=24 hours	From t=12 to t=24 hours after IMP administration
Secondary	AUCLIS 12-30h	Area under the insulin lispro concentration-time curve from t=12 to t=30 hours	From t=12 to t=30 hours after IMP administration
Secondary	AUCLIS 0-30h	Area under the insulin lispro concentration-time curve from t=0 to t=30 hours	From t=0 to t=30 hours after IMP administration
Secondary	CmaxLIS	Maximum concentration of insulin lispro	From t=0 to t=30 hours after IMP administration
Secondary	tmaxLIS	Time to maximum insulin lispro concentration	From t=0 to t=30 hours after IMP administration
Secondary	Adverse Events	Incidence of Adverse Events	From the first IMP administration to the follow-up visit (i.e. up to 14 weeks)
Secondary	Local tolerability	Incidence of Injection Site Reactions	From the first IMP administration to the follow-up visit (i.e. up to 14 weeks)