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

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Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Type 2 Diabetes

Interventions

Euglycemic clamp with BC Combo THDB0207DRUG

Administration of a single dose of BC Combo THDB0207 during an euglycemic clamp procedure.

Euglycemic clamp with Humalog® Mix25DRUG

Administration of a single dose of Humalog® Mix25 during an euglycemic clamp procedure.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

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

Locations (1)

Profil Institut für Stoffwechselforschung GmbH

Neuss, Germany

Outcomes

Primary Outcomes

AUCTOTAL0-last

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

CmaxTOTAL

Maximum total insulin concentration

Time frame: From t=0 to t=30 hours after IMP administration

Secondary Outcomes

AUCGIR 0-last

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

GIRmax

Maximum glucose infusion rate

Time frame: From t=0 to t=30 hours after IMP administration

tGIRmax

Time to maximum glucose infusion rate

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: From t=0 to t=30 hours after IMP administration

Data from ClinicalTrials.gov

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AUCTOTAL 0-1h

Area under the total insulin concentration-time curve from t=0 to t=1 hour

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: From t=0 to t=30 hours

CTOTALmax

Maximum insulin concentration

Time frame: From t=0 to t=30 hours after IMP administration

tmaxTOTAL

Time to maximum total insulin concentration

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: From t=0 to t=30 hours after IMP administration

CmaxGLA

Maximum concentration of insulin glargine

Time frame: From t=0 to t=30 hours after IMP administration

tmaxGLA

Time to maximum insulin glargine concentration

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: From t=0 to t=30 hours after IMP administration

CmaxLIS

Maximum concentration of insulin lispro

Time frame: From t=0 to t=30 hours after IMP administration

tmaxLIS

Time to maximum insulin lispro concentration

Time frame: From t=0 to t=30 hours after IMP administration

Adverse Events

Incidence of Adverse Events

Time frame: From the first IMP administration to the follow-up visit (i.e. up to 14 weeks)

Local tolerability

Incidence of Injection Site Reactions

Time frame: From the first IMP administration to the follow-up visit (i.e. up to 14 weeks)