Back to resultsA Trial Comparing the Pharmacodynamics and Pharmacokinetics of BC Combo THDB0207 and Lantus® and Humalog® in Subjects With Type 1 Diabetes
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Euglycemic clamp with BC Combo THDB0207
Euglycemic clamp with Lantus®
Euglycemic clamp with Humalog®
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes
Eligibility Criteria
Inclusion Criteria:
- Type 1 diabetes mellitus (as diagnosed clinically) for ≥ 12 months
- HbA1c ≤8.5%
- Total insulin dose of < 1.2 U/kg/day
- BMI between 20.0 and 29.9 kg/m2 (both inclusive)
- Treated with insulin regimen for ≥ 12 months prior to screening
- Using multiple dosing insulin therapy (MDI) with basal and bolus insulin or insulin pump therapy (continuous subcutaneous insulin infusion, CSII)
- Fasting C-peptide <= 0.30 nmol/L
Exclusion Criteria:
- Known or suspected hypersensitivity to the IMPs or any of the excipients or to any component of the IMP formulation.
- Type 2 diabetes mellitus
- Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists (e.g. exenatide, liraglutide)
- 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 >139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 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.
- More than one episode of severe hypoglycaemia with seizure, coma or requiring assistance of another person during the past 6 months or hypoglycaemia unawareness as judged by the investigator
- Women of childbearing potential who are not using a highly effective contraceptive method.
Sites / Locations
- Profil Institut für Stoffwechselforschung GmbH
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
BC Combo THDB0207
Lantus®
Humalog®
Arm Description
Single administration of BC Combo THDB0207
Single administration of Lantus®
Single administration of Humalog®
Outcomes
Primary Outcome Measures
AUCGIR 0-6h
Area under the glucose infusion rate curve until 6 hours after dosing of BC Combo THDB0207 and Lantus®
AUCGIR 6-24h
Area under the glucose infusion rate curve from 6 hours to 24 hours after dosing of BC Combo THDB0207 and Humalog®
Secondary Outcome Measures
AUCGIR 0-last
Area under the glucose infusion rate curve from 0 hours until the end of clamp
AUCGIR 0-4h
Area under the glucose infusion rate curve from 0 hours until 4 hours
GIRmax
Maximum glucose infusion rate
tGIRmax
Time to maximum glucose infusion rate
tonset of action
Time until Plasma Glucose (PG) has decreased by at least 5 mg/dL from the baseline PG value.
AUCINS 0-6h
Area under the insulin concentration-time curve from 0 hours until 6 hours
AUCINS 0-24h
Area under the insulin concentration-time curve from 0 hours until 24 hours
AUCINS 6-24h
Area under the insulin concentration-time curve from 6 hours until 24 hours
AUCINS 4-12h
Area under the insulin concentration-time curve from 4 hours until 12 hours
AUCINS 0-4h
Area under the insulin concentration-time curve from 0 hours until 4 hours
AUCINSlast
Area under the insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
Cmax INS
Maximum insulin concentration
RBA
Relative bioavailability of BC Combo THDB0207 vs Humalog®
AUCBC 0-12h
Area under the BC449 concentration-time curve from 0 hours until 12 hours
AUCBC 0-24h
Area under the BC449 concentration-time curve from 0 hours until 24 hours
AUCBC 0-last
Area under the BC449 concentration-time curve from t=0 to the last measured BC449 concentration above LLOQ
Adverse Events
Incidence of Adverse Events
Local tolerability
Incidence of injection site reactions
Full Information
NCT ID
NCT05373199
First Posted
May 4, 2022
Last Updated
September 14, 2023
Sponsor
Adocia
Collaborators
Tonghua Dongbao Pharmaceutical Co.,Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05373199
Brief Title
A Trial Comparing the Pharmacodynamics and Pharmacokinetics of BC Combo THDB0207 and Lantus® and Humalog® in Subjects With Type 1 Diabetes
Official Title
A Trial Comparing the Pharmacodynamics and Pharmacokinetics of BC Combo THDB0207 and Lantus® and Humalog® in Subjects With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 12, 2022 (Actual)
Primary Completion Date
October 28, 2022 (Actual)
Study Completion Date
October 28, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adocia
Collaborators
Tonghua Dongbao Pharmaceutical Co.,Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomised, double-blind, three-period crossover euglycaemic clamp trial comparing pharmacokinetics and pharmacodynamics of BC Combo THDB0207 and Lantus® and Humalog® in subjects with type 1 diabetes.
Each subject will be randomly allocated to one of the 6 treatment sequences and will be administered single subcutaneous doses of BC Combo THDB0207, Lantus®, and Humalog® at three separate dosing visits.
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 24-hour clamp procedures have been terminated. Patients will return to the clinical trial centre for outpatient blood sampling visits for analysis of BC449 excipient until 144 hours after each dosing.
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 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 24 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 (INS) concentration (insulin glargine + insulin glargine-M1 + insulin glargine-M2 + insulin lispro).
The investigation of PK properties of the BC449 excipient after dosing with BC Combo THDB0207 will be based on blood samples collected during the clamp procedure and at daily outpatient visits until 144 hours after dose administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Three-period crossover
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BC Combo THDB0207
Arm Type
Experimental
Arm Description
Single administration of BC Combo THDB0207
Arm Title
Lantus®
Arm Type
Active Comparator
Arm Description
Single administration of Lantus®
Arm Title
Humalog®
Arm Type
Active Comparator
Arm Description
Single administration of Humalog®
Intervention Type
Drug
Intervention Name(s)
Euglycemic clamp with BC Combo THDB0207
Intervention Description
Administration of a single dose of BC Combo THDB0207 during an euglycemic clamp procedure.
Intervention Type
Drug
Intervention Name(s)
Euglycemic clamp with Lantus®
Intervention Description
Administration of a single dose of Lantus® during an euglycemic clamp procedure.
Intervention Type
Drug
Intervention Name(s)
Euglycemic clamp with Humalog®
Intervention Description
Administration of a single dose of Humalog® during an euglycemic clamp procedure.
Primary Outcome Measure Information:
Title
AUCGIR 0-6h
Description
Area under the glucose infusion rate curve until 6 hours after dosing of BC Combo THDB0207 and Lantus®
Time Frame
From t=0 to t=6 hours after IMP administration
Title
AUCGIR 6-24h
Description
Area under the glucose infusion rate curve from 6 hours to 24 hours after dosing of BC Combo THDB0207 and Humalog®
Time Frame
From t=6 to t=24 hours after IMP administration
Secondary Outcome Measure Information:
Title
AUCGIR 0-last
Description
Area under the glucose infusion rate curve from 0 hours until the end of clamp
Time Frame
From t=0 to t=24 hours after IMP administration
Title
AUCGIR 0-4h
Description
Area under the glucose infusion rate curve from 0 hours until 4 hours
Time Frame
From t=0 to t=4 hours after IMP administration
Title
GIRmax
Description
Maximum glucose infusion rate
Time Frame
From t=0 to t=24 hours
Title
tGIRmax
Description
Time to maximum glucose infusion rate
Time Frame
From t=0 to t=24 hours
Title
tonset of action
Description
Time until Plasma Glucose (PG) has decreased by at least 5 mg/dL from the baseline PG value.
Time Frame
From t=0 to t=24 hours after IMP administration
Title
AUCINS 0-6h
Description
Area under the insulin concentration-time curve from 0 hours until 6 hours
Time Frame
From t=0 to t=6 hours after IMP administration
Title
AUCINS 0-24h
Description
Area under the insulin concentration-time curve from 0 hours until 24 hours
Time Frame
From t=0 to t=24 hours after IMP administration
Title
AUCINS 6-24h
Description
Area under the insulin concentration-time curve from 6 hours until 24 hours
Time Frame
From t=6 to t=24 hours after IMP administration
Title
AUCINS 4-12h
Description
Area under the insulin concentration-time curve from 4 hours until 12 hours
Time Frame
From t=4 to t=12 hours after IMP administration
Title
AUCINS 0-4h
Description
Area under the insulin concentration-time curve from 0 hours until 4 hours
Time Frame
From t=0 to t=4 hours after IMP administration
Title
AUCINSlast
Description
Area under the insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
Time Frame
From t=0 to t=24 hours
Title
Cmax INS
Description
Maximum insulin concentration
Time Frame
From t=0 to t=24 hours after IMP administration
Title
RBA
Description
Relative bioavailability of BC Combo THDB0207 vs Humalog®
Time Frame
From t=0 to t=24 hours after IMP administration
Title
AUCBC 0-12h
Description
Area under the BC449 concentration-time curve from 0 hours until 12 hours
Time Frame
From t=0 to t=12 hours after IMP administration
Title
AUCBC 0-24h
Description
Area under the BC449 concentration-time curve from 0 hours until 24 hours
Time Frame
From t=0 to t=24 hours after IMP administration
Title
AUCBC 0-last
Description
Area under the BC449 concentration-time curve from t=0 to the last measured BC449 concentration above LLOQ
Time Frame
From t=0 to t=144 hours after IMP administration
Title
Adverse Events
Description
Incidence of Adverse Events
Time Frame
From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)
Title
Local tolerability
Description
Incidence of injection site reactions
Time Frame
From the first IMP administration to the follow-up visit (i.e. up to 11 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Type 1 diabetes mellitus (as diagnosed clinically) for ≥ 12 months
HbA1c ≤8.5%
Total insulin dose of < 1.2 U/kg/day
BMI between 20.0 and 29.9 kg/m2 (both inclusive)
Treated with insulin regimen for ≥ 12 months prior to screening
Using multiple dosing insulin therapy (MDI) with basal and bolus insulin or insulin pump therapy (continuous subcutaneous insulin infusion, CSII)
Fasting C-peptide <= 0.30 nmol/L
Exclusion Criteria:
Known or suspected hypersensitivity to the IMPs or any of the excipients or to any component of the IMP formulation.
Type 2 diabetes mellitus
Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists (e.g. exenatide, liraglutide)
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 >139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 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.
More than one episode of severe hypoglycaemia with seizure, coma or requiring assistance of another person during the past 6 months or hypoglycaemia unawareness as judged by the investigator
Women of childbearing potential who are not using a highly effective contraceptive method.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Stoffel, MD
Organizational Affiliation
Profil Institut für Stoffwechselforschung GmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Profil Institut für Stoffwechselforschung GmbH
City
Neuss
ZIP/Postal Code
41460
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
A Trial Comparing the Pharmacodynamics and Pharmacokinetics of BC Combo THDB0207 and Lantus® and Humalog® in Subjects With Type 1 Diabetes
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