A Randomised, Double Blind, Crossover Euglycaemic Clamp Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Adocia
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- AUCGIR.0-1h
研究概览
简要总结
This is a single-centre, randomised, double-blind, 4-way crossover, 4-treatment, euglycaemic clamp study in subjects with Type 1 Diabetes Mellitus (T1DM). Each subject will be randomly allocated to one of four treatment sequences. Each sequence comprises one single dose of each of four IMPs. IMP1 and IMP2 are BioChaperone lispro formulations. They have the same composition and correspond to different development stages of a unique product which is BioChaperone insulin lispro; between them, improvements were made to prepare industrial production. Comparators (IMP3 and IMP4) are US-approved Humalog® and EU-approved Humalog®. All IMPs will be dosed at 0.2 U/Kg of insulin lispro on 4 dosing visits separated by a washout period of 5 to 15 days.
The trial will compare the characteristics of BioChaperone insulin lispro fully liquid (IMP2) formulation to US-approved Humalog and EU-approved Humalog.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with type 1 Diabetes Mellitus
- •Body Mass Index (BMI) between 18.5 and 28.5 kg/m^2, both inclusive
- •HbA1c <= 75 mmol/mol (<=9.0%).
- •Fasting negative C-peptide (<= 0.30 nmol/L).
- •Total insulin dose of < 1.2 (I)U/kg/day.
- •Stable insulin regimen (with respect to safety of the subject and scientific integrity of the study) using continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI) for at least 2 months.
排除标准
- •Known or suspected hypersensitivity to IMP(s) or related products.
- •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.
- •History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
- •Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator.
- •Any history or presence of clinically relevant comorbidity capable of constituting a risk for the subject when participating in the trial or of interfering with the interpretation of data.
- •Signs of acute illness as judged by the Investigator.
- •Any serious systemic infectious disease during four weeks prior to first dosing of the trial drug, as judged by the Investigator.
- •Clinically significant abnormal screening laboratory tests, as judged by the Investigator.
- •Proliferative retinopathy or maculopathy as judged by the Investigator based on a recent (<1.5 years) ophthalmologic examination.
- •Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists within 3 months prior to screening.
研究组 & 干预措施
BioChaperone insulin lispro reconstituted with Humalog® (IMP1)
Subcutaneous administration of Biochaperone insulin lispro formulation made from a freeze-dried of BioChaperone reconstituted with Humalog® at a dose of 0.2 U/Kg Body Weight (BW).
干预措施: Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1) (Drug)
Ready-to-use BioChaperone insulin lispro (IMP2)
Subcutaneous administration of ready-to-use Biochaperone insulin lispro formulation at a dose of 0.2 U/Kg BW.
干预措施: Administration of Ready-to-use BioChaperone insulin lispro (IMP2) (Drug)
US-approved Humalog® (IMP3)
Subcutaneous administration of US-approved Humalog® at a dose of 0.2 U/Kg BW.
干预措施: Administration of US-approved Humalog® (IMP3) (Drug)
EU-approved Humalog® (IMP4)
Subcutaneous administration of EU-approved Humalog® at a dose of 0.2 U/Kg BW.
干预措施: Administration of EU-approved Humalog® (IMP4) (Drug)
结局指标
主要结局
AUCGIR.0-1h
时间窗: From t=0 to t=1 hour after IMP administration
Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration
AUCGIR.0-12h
时间窗: From t=0 to t=12 hours after IMP administration
Area under the glucose infusion rate-time curve from time 0 until end of clamp
AUCLIS.0-1h
时间窗: From t=0 to t=1 hour after IMP administration
Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration
AUCLIS.0-12h
时间窗: From t=0 to t=12 hours after IMP administration
Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration
次要结局
- t50%-LIS (early)(From t=0 to t=12 hours after IMP administration)
- Cmax.LIS(From t=0 to t=12 hours after IMP administration)
- tmax.LIS(From t=0 to t=12 hours after IMP administration)
- AUCLIS.2-6h(From t=2 to t=6hours after IMP administration)
- tmax.GIR(From t=0 to t=12 hours after IMP administration)
- GIRmax(From t=0 to t=12 hours after IMP administration)
- AUCGIR.4-8h(From t=4 to t=8 hours after IMP administration)