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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Euglycemic clamp with BC Combo THDB0207; Drug: Euglycemic clamp with Humalog® Mix25

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. 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• 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: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BC Combo THDB0207 Low dose; Single administration of BC Combo THDB0207 (Low dose)	Drug: Euglycemic clamp with BC Combo THDB0207; Administration of a single dose of BC Combo THDB0207 during an euglycemic clamp procedure.
Experimental: BC Combo THDB0207 Medium dose; Single administration of BC Combo THDB0207 (Medium dose)	Drug: Euglycemic clamp with BC Combo THDB0207; Administration of a single dose of BC Combo THDB0207 during an euglycemic clamp procedure.
Experimental: BC Combo THDB0207 High dose; Single administration of BC Combo THDB0207 (High dose)	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
CmaxTOTAL	Maximum total insulin concentration	From t=0 to t=30 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
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
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
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
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
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
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
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
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
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
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
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
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
CTOTALmax	Maximum insulin concentration	From t=0 to t=30 hours after IMP administration
tmaxTOTAL	Time to maximum total insulin concentration	From t=0 to t=30 hours after IMP administration
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
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
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
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
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
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
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
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
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
CmaxGLA	Maximum concentration of insulin glargine	From t=0 to t=30 hours after IMP administration
tmaxGLA	Time to maximum insulin glargine concentration	From t=0 to t=30 hours after IMP administration
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
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
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
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
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
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
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
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
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
CmaxLIS	Maximum concentration of insulin lispro	From t=0 to t=30 hours after IMP administration
tmaxLIS	Time to maximum insulin lispro concentration	From t=0 to t=30 hours after IMP administration
Adverse Events	Incidence of Adverse Events	From the first IMP administration to the follow-up visit (i.e. up to 14 weeks)
Local tolerability	Incidence of Injection Site Reactions	From the first IMP administration to the follow-up visit (i.e. up to 14 weeks)

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): January 2, 2023
• Study Completion (Actual): January 2, 2023

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): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: CT048-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