A Trial Investigating the Dose Linearity and Safety of BC Combo THDB0207 in Subjects With Type 2 Diabetes
- Conditions
- Type 2 Diabetes
- Interventions
- Drug: Euglycemic clamp with BC Combo THDB0207Drug: Euglycemic clamp with Humalog® Mix25
- Registration Number
- NCT05373212
- Lead Sponsor
- Adocia
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description BC Combo THDB0207 Medium dose Euglycemic clamp with BC Combo THDB0207 Single administration of BC Combo THDB0207 (Medium dose) BC Combo THDB0207 Low dose Euglycemic clamp with BC Combo THDB0207 Single administration of BC Combo THDB0207 (Low dose) BC Combo THDB0207 High dose Euglycemic clamp with BC Combo THDB0207 Single administration of BC Combo THDB0207 (High dose) Humalog® Mix25 Euglycemic clamp with Humalog® Mix25 Single administration of Humalog® Mix25
- Primary Outcome Measures
Name Time Method AUCTOTAL0-last From t=0 to t=30 hours after IMP administration Area under the total insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
CmaxTOTAL From t=0 to t=30 hours after IMP administration Maximum total insulin concentration
- Secondary Outcome Measures
Name Time Method AUCTOTAL 12-24h From t=12 to t=24 hours Area under the total insulin concentration-time curve from t=12 to t=24 hours
AUCLIS 12-24h From t=12 to t=24 hours after IMP administration Area under the insulin lispro concentration-time curve from t=12 to t=24 hours
AUCGIR 0-last From t=0 to t=30 hours after IMP administration Area under the glucose infusion rate curve from 0 hours until the end of clamp
GIRmax From t=0 to t=30 hours after IMP administration Maximum glucose infusion rate
AUCTOTAL 6-24h From t=6 to t=24 hours Area under the total insulin concentration-time curve from t=6 to t=24 hours
AUCTOTAL 0-2h From t=0 to t=2 hours Area under the total insulin concentration-time curve from t=0 to t=2 hours
AUCTOTAL 0-6h From t=0 to t=6 hours Area under the total insulin concentration-time curve from t=0 to t=6 hours
AUCTOTAL 12-30h From t=12 to t=30 hours Area under the total insulin concentration-time curve from t=12 to t=30 hours
AUCTOTAL 0-30h From t=0 to t=30 hours Area under the total insulin concentration-time curve from t=0 to t=30 hours
CTOTALmax From t=0 to t=30 hours after IMP administration Maximum insulin concentration
tmaxTOTAL From t=0 to t=30 hours after IMP administration Time to maximum total insulin concentration
AUCGLA 0-last From t=0 to t=30 hours after IMP administration Area under the insulin glargine concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
AUCGLA 2-6h From t=2 to t=6 hours after IMP administration Area under the insulin glargine concentration-time curve from t=2 to t=6 hours
AUCGLA 12-24h From t=12 to t=24 hours after IMP administration Area under the insulin glargine concentration-time curve from t=12 to t=24 hours
AUCGLA 0-30h From t=0 to t=30 hours after IMP administration Area under the insulin glargine concentration-time curve from t=0 to t=30 hours
Tonset of action From t=0 to t=30 hours after IMP administration Time until Plasma Glucose (PG) has decreased by at least 5 mg/dL from the baseline PG value.
AUCTOTALlast From t=0 to t=30 hours after IMP administration Area under the insulin concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
AUCTOTAL 0-1h From t=0 to t=1 hour Area under the total insulin concentration-time curve from t=0 to t=1 hour
AUCGLA 12-30h From t=12 to t=30 hours after IMP administration Area under the insulin glargine concentration-time curve from t=12 to t=30 hours
AUCGIR 0-6h From t=0 to t=6 hours Area under the glucose infusion rate curve from t=0 hours to t=6 hours
AUCGLA 0-6h From t=0 to t=6 hours after IMP administration Area under the insulin glargine concentration-time curve from t=0 to t=6 hours
AUCLIS0-last From t=0 to t=30 hours after IMP administration Area under the insulin lispro concentration-time curve from t=0 to the last measured insulin concentration above LLOQ
AUCLIS 0-1h From t=0 to t=1 hour after IMP administration Area under the insulin lispro concentration-time curve from t=0 to t=1 hour
AUCLIS 0-2h From t=0 to t=2 hours after IMP administration Area under the insulin lispro concentration-time curve from t=0 to t=2 hours
AUCLIS 0-6h From t=0 to t=6 hours after IMP administration Area under the insulin lispro concentration-time curve from t=0 to t=6 hours
AUCLIS 2-6h From t=2 to t=6 hours after IMP administration Area under the insulin lispro concentration-time curve from t=2 to t=6 hours
tGIRmax From t=0 to t=30 hours after IMP administration Time to maximum glucose infusion rate
AUCTOTAL 2-6h From t=2 to t=6 hours Area under the total insulin concentration-time curve from t=2 to t=6 hours
AUCTOTAL 6-12h From t=6 to t=12 hours Area under the total insulin concentration-time curve from t=6 to t=12 hours
AUCGLA 0-1h From t=0 to t=1 hour after IMP administration Area under the insulin glargine concentration-time curve from t=0 to t=1 hour
AUCGLA 0-2h From t=0 to t=2 hours after IMP administration Area under the insulin glargine concentration-time curve from t=0 to t=2 hours
AUCGLA 6-12h From t=6 to t=12 hours after IMP administration Area under the insulin glargine concentration-time curve from t=6 to t=12 hours
CmaxGLA From t=0 to t=30 hours after IMP administration Maximum concentration of insulin glargine
tmaxGLA From t=0 to t=30 hours after IMP administration Time to maximum insulin glargine concentration
CmaxLIS From t=0 to t=30 hours after IMP administration Maximum concentration of insulin lispro
AUCLIS 6-12h From t=6 to t=12 hours after IMP administration Area under the insulin lispro concentration-time curve from t=6 to t=12 hours
AUCLIS 12-30h From t=12 to t=30 hours after IMP administration Area under the insulin lispro concentration-time curve from t=12 to t=30 hours
AUCLIS 0-30h From t=0 to t=30 hours after IMP administration Area under the insulin lispro concentration-time curve from t=0 to t=30 hours
Adverse Events From the first IMP administration to the follow-up visit (i.e. up to 14 weeks) Incidence of Adverse Events
tmaxLIS From t=0 to t=30 hours after IMP administration Time to maximum insulin lispro concentration
Local tolerability From the first IMP administration to the follow-up visit (i.e. up to 14 weeks) Incidence of Injection Site Reactions
Trial Locations
- Locations (1)
Profil Institut für Stoffwechselforschung GmbH
🇩🇪Neuss, Germany