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

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.

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.

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