Back to resultsA Trial Investigating the Dose Linearity and Safety of BC Combo THDB0207 in Subjects With Type 2 Diabetes
Primary Purpose
Type 2 Diabetes
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Euglycemic clamp with BC Combo THDB0207
Euglycemic clamp with Humalog® Mix25
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes
Eligibility Criteria
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
Sites / Locations
- Profil Institut für Stoffwechselforschung GmbH
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
BC Combo THDB0207 Low dose
BC Combo THDB0207 Medium dose
BC Combo THDB0207 High dose
Humalog® Mix25
Arm Description
Single administration of BC Combo THDB0207 (Low dose)
Single administration of BC Combo THDB0207 (Medium dose)
Single administration of BC Combo THDB0207 (High dose)
Single administration of Humalog® Mix25
Outcomes
Primary Outcome Measures
AUCTOTAL0-last
Area under the total insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
CmaxTOTAL
Maximum total insulin concentration
Secondary Outcome Measures
AUCGIR 0-last
Area under the glucose infusion rate curve from 0 hours until the end of clamp
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.
AUCGIR 0-6h
Area under the glucose infusion rate curve from t=0 hours to t=6 hours
AUCTOTALlast
Area under the insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
AUCTOTAL 0-1h
Area under the total insulin concentration-time curve 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
AUCTOTAL 0-6h
Area under the total insulin concentration-time curve 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
AUCTOTAL 6-12h
Area under the total insulin concentration-time curve 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
AUCTOTAL 12-24h
Area under the total insulin concentration-time curve 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
AUCTOTAL 0-30h
Area under the total insulin concentration-time curve from t=0 to t=30 hours
CTOTALmax
Maximum insulin concentration
tmaxTOTAL
Time to maximum total insulin concentration
AUCGLA 0-last
Area under the insulin glargine concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
AUCGLA 0-1h
Area under the insulin glargine concentration-time curve from t=0 to t=1 hour
AUCGLA 0-2h
Area under the insulin glargine concentration-time curve from t=0 to t=2 hours
AUCGLA 0-6h
Area under the insulin glargine concentration-time curve from t=0 to t=6 hours
AUCGLA 2-6h
Area under the insulin glargine concentration-time curve from t=2 to t=6 hours
AUCGLA 6-12h
Area under the insulin glargine concentration-time curve from t=6 to t=12 hours
AUCGLA 12-24h
Area under the insulin glargine concentration-time curve from t=12 to t=24 hours
AUCGLA 12-30h
Area under the insulin glargine concentration-time curve from t=12 to t=30 hours
AUCGLA 0-30h
Area under the insulin glargine concentration-time curve from t=0 to t=30 hours
CmaxGLA
Maximum concentration of insulin glargine
tmaxGLA
Time to maximum insulin glargine concentration
AUCLIS0-last
Area under the insulin lispro concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
AUCLIS 0-1h
Area under the insulin lispro concentration-time curve from t=0 to t=1 hour
AUCLIS 0-2h
Area under the insulin lispro concentration-time curve from t=0 to t=2 hours
AUCLIS 0-6h
Area under the insulin lispro concentration-time curve from t=0 to t=6 hours
AUCLIS 2-6h
Area under the insulin lispro concentration-time curve from t=2 to t=6 hours
AUCLIS 6-12h
Area under the insulin lispro concentration-time curve from t=6 to t=12 hours
AUCLIS 12-24h
Area under the insulin lispro concentration-time curve from t=12 to t=24 hours
AUCLIS 12-30h
Area under the insulin lispro concentration-time curve from t=12 to t=30 hours
AUCLIS 0-30h
Area under the insulin lispro concentration-time curve from t=0 to t=30 hours
CmaxLIS
Maximum concentration of insulin lispro
tmaxLIS
Time to maximum insulin lispro concentration
Adverse Events
Incidence of Adverse Events
Local tolerability
Incidence of Injection Site Reactions
Full Information
NCT ID
NCT05373212
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
NCT05373212
Brief Title
A Trial Investigating the Dose Linearity and Safety of BC Combo THDB0207 in Subjects With Type 2 Diabetes
Official Title
A Trial Investigating the Dose Linearity and Safety of BC Combo THDB0207 in Subjects With Type 2 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
January 2, 2023 (Actual)
Study Completion Date
January 2, 2023 (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, 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Four-period crossover
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BC Combo THDB0207 Low dose
Arm Type
Experimental
Arm Description
Single administration of BC Combo THDB0207 (Low dose)
Arm Title
BC Combo THDB0207 Medium dose
Arm Type
Experimental
Arm Description
Single administration of BC Combo THDB0207 (Medium dose)
Arm Title
BC Combo THDB0207 High dose
Arm Type
Experimental
Arm Description
Single administration of BC Combo THDB0207 (High dose)
Arm Title
Humalog® Mix25
Arm Type
Active Comparator
Arm Description
Single administration of Humalog® Mix25
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 Humalog® Mix25
Intervention Description
Administration of a single dose of Humalog® Mix25 during an euglycemic clamp procedure.
Primary Outcome Measure Information:
Title
AUCTOTAL0-last
Description
Area under the total insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
Time Frame
From t=0 to t=30 hours after IMP administration
Title
CmaxTOTAL
Description
Maximum total insulin concentration
Time Frame
From t=0 to t=30 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=30 hours after IMP administration
Title
GIRmax
Description
Maximum glucose infusion rate
Time Frame
From t=0 to t=30 hours after IMP administration
Title
tGIRmax
Description
Time to maximum glucose infusion rate
Time Frame
From t=0 to t=30 hours after IMP administration
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=30 hours after IMP administration
Title
AUCGIR 0-6h
Description
Area under the glucose infusion rate curve from t=0 hours to t=6 hours
Time Frame
From t=0 to t=6 hours
Title
AUCTOTALlast
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=30 hours after IMP administration
Title
AUCTOTAL 0-1h
Description
Area under the total insulin concentration-time curve from t=0 to t=1 hour
Time Frame
From t=0 to t=1 hour
Title
AUCTOTAL 0-2h
Description
Area under the total insulin concentration-time curve from t=0 to t=2 hours
Time Frame
From t=0 to t=2 hours
Title
AUCTOTAL 0-6h
Description
Area under the total insulin concentration-time curve from t=0 to t=6 hours
Time Frame
From t=0 to t=6 hours
Title
AUCTOTAL 2-6h
Description
Area under the total insulin concentration-time curve from t=2 to t=6 hours
Time Frame
From t=2 to t=6 hours
Title
AUCTOTAL 6-12h
Description
Area under the total insulin concentration-time curve from t=6 to t=12 hours
Time Frame
From t=6 to t=12 hours
Title
AUCTOTAL 6-24h
Description
Area under the total insulin concentration-time curve from t=6 to t=24 hours
Time Frame
From t=6 to t=24 hours
Title
AUCTOTAL 12-24h
Description
Area under the total insulin concentration-time curve from t=12 to t=24 hours
Time Frame
From t=12 to t=24 hours
Title
AUCTOTAL 12-30h
Description
Area under the total insulin concentration-time curve from t=12 to t=30 hours
Time Frame
From t=12 to t=30 hours
Title
AUCTOTAL 0-30h
Description
Area under the total insulin concentration-time curve from t=0 to t=30 hours
Time Frame
From t=0 to t=30 hours
Title
CTOTALmax
Description
Maximum insulin concentration
Time Frame
From t=0 to t=30 hours after IMP administration
Title
tmaxTOTAL
Description
Time to maximum total insulin concentration
Time Frame
From t=0 to t=30 hours after IMP administration
Title
AUCGLA 0-last
Description
Area under the insulin glargine concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
Time Frame
From t=0 to t=30 hours after IMP administration
Title
AUCGLA 0-1h
Description
Area under the insulin glargine concentration-time curve from t=0 to t=1 hour
Time Frame
From t=0 to t=1 hour after IMP administration
Title
AUCGLA 0-2h
Description
Area under the insulin glargine concentration-time curve from t=0 to t=2 hours
Time Frame
From t=0 to t=2 hours after IMP administration
Title
AUCGLA 0-6h
Description
Area under the insulin glargine concentration-time curve from t=0 to t=6 hours
Time Frame
From t=0 to t=6 hours after IMP administration
Title
AUCGLA 2-6h
Description
Area under the insulin glargine concentration-time curve from t=2 to t=6 hours
Time Frame
From t=2 to t=6 hours after IMP administration
Title
AUCGLA 6-12h
Description
Area under the insulin glargine concentration-time curve from t=6 to t=12 hours
Time Frame
From t=6 to t=12 hours after IMP administration
Title
AUCGLA 12-24h
Description
Area under the insulin glargine concentration-time curve from t=12 to t=24 hours
Time Frame
From t=12 to t=24 hours after IMP administration
Title
AUCGLA 12-30h
Description
Area under the insulin glargine concentration-time curve from t=12 to t=30 hours
Time Frame
From t=12 to t=30 hours after IMP administration
Title
AUCGLA 0-30h
Description
Area under the insulin glargine concentration-time curve from t=0 to t=30 hours
Time Frame
From t=0 to t=30 hours after IMP administration
Title
CmaxGLA
Description
Maximum concentration of insulin glargine
Time Frame
From t=0 to t=30 hours after IMP administration
Title
tmaxGLA
Description
Time to maximum insulin glargine concentration
Time Frame
From t=0 to t=30 hours after IMP administration
Title
AUCLIS0-last
Description
Area under the insulin lispro concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
Time Frame
From t=0 to t=30 hours after IMP administration
Title
AUCLIS 0-1h
Description
Area under the insulin lispro concentration-time curve from t=0 to t=1 hour
Time Frame
From t=0 to t=1 hour after IMP administration
Title
AUCLIS 0-2h
Description
Area under the insulin lispro concentration-time curve from t=0 to t=2 hours
Time Frame
From t=0 to t=2 hours after IMP administration
Title
AUCLIS 0-6h
Description
Area under the insulin lispro concentration-time curve from t=0 to t=6 hours
Time Frame
From t=0 to t=6 hours after IMP administration
Title
AUCLIS 2-6h
Description
Area under the insulin lispro concentration-time curve from t=2 to t=6 hours
Time Frame
From t=2 to t=6 hours after IMP administration
Title
AUCLIS 6-12h
Description
Area under the insulin lispro concentration-time curve from t=6 to t=12 hours
Time Frame
From t=6 to t=12 hours after IMP administration
Title
AUCLIS 12-24h
Description
Area under the insulin lispro concentration-time curve from t=12 to t=24 hours
Time Frame
From t=12 to t=24 hours after IMP administration
Title
AUCLIS 12-30h
Description
Area under the insulin lispro concentration-time curve from t=12 to t=30 hours
Time Frame
From t=12 to t=30 hours after IMP administration
Title
AUCLIS 0-30h
Description
Area under the insulin lispro concentration-time curve from t=0 to t=30 hours
Time Frame
From t=0 to t=30 hours after IMP administration
Title
CmaxLIS
Description
Maximum concentration of insulin lispro
Time Frame
From t=0 to t=30 hours after IMP administration
Title
tmaxLIS
Description
Time to maximum insulin lispro concentration
Time Frame
From t=0 to t=30 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 14 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 14 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oliver Klein, 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 Investigating the Dose Linearity and Safety of BC Combo THDB0207 in Subjects With Type 2 Diabetes
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