A Randomized, Double-blind, Single-dose, 2-Treatment, 2-Period, 2-Sequence Crossover Bioequivalence Study Comparing Two Formulations of Insulin Glulisine (Insulin Glulisine 300 Units/mL Versus Insulin Glulisine 100 Units/mL Marketed as Apidra® 100 Units/mL) Using the Euglycemic Clamp Technique, in Patients With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Assessment of PK parameter: maximum observed insulin concentration
研究概览
简要总结
Primary Objective:
To demonstrate bioequivalence between insulin glulisine given as 300 Units/mL test formulation and insulin glulisine 100 Units/mL reference formulation after a single subcutaneous (SC) dose.
Secondary Objectives:
- To assess the pharmacodynamic (PD) profiles and further pharmacokinetic (PK) characteristics of insulin glulisine U300 in comparison to insulin glulisine U100 after a single SC dose.
- To assess safety and tolerability of the test and the reference formulation of insulin glulisine.
详细描述
The study duration per patient will be 18 to 62 days and will consist of a 4 to 28 days of screening period, a treatment period of 2 days, a washout between dosing occasions of 5-18 days, and follow up visit 7-14 days after last dosing.
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
- Double (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Insulin glulisine (U300) - Test formulation
Insulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Insulin glulisine (U300) (Drug)
Insulin glulisine (U300) - Test formulation
Insulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Insulin aspart (Drug)
Insulin glulisine (U300) - Test formulation
Insulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: NPH insulin (Drug)
Insulin glulisine (U300) - Test formulation
Insulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Glucagon (Drug)
Insulin glulisine (U300) - Test formulation
Insulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Glucose (Drug)
Insulin glulisine (U300) - Test formulation
Insulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Heparin (Drug)
Insulin glulisine - Reference formulation
Insulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Insulin glulisine (Drug)
Insulin glulisine - Reference formulation
Insulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Insulin aspart (Drug)
Insulin glulisine - Reference formulation
Insulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: NPH insulin (Drug)
Insulin glulisine - Reference formulation
Insulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Glucagon (Drug)
Insulin glulisine - Reference formulation
Insulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Glucose (Drug)
Insulin glulisine - Reference formulation
Insulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
干预措施: Heparin (Drug)
结局指标
主要结局
Assessment of PK parameter: maximum observed insulin concentration
时间窗: 10 hours
Assessment of PK parameter: area under the concentration time curve
时间窗: 10 hours
次要结局
- Assessment of PK parameter: time to reach Cmax (INS-tmax)(10 hours)
- Assessment of PK parameter: terminal half-life (INS-t1/2z)(10 hours)
- Assessment of PD parameter: area under the body weight standardized glucose infusion rate (GIR) versus time curve from 0 to 10 hours (GIR-AUC0-10)(10 hours)
- Assessment of PD parameter: maximum smoothed body weight standardized GIR (GIRmax)(10 hours)
- Assessment of PD parameter: time to GIRmax (GIR-tmax)(10 hours)
- Duration of blood glucose control under clamp conditions - time(10 hours)
- Number of patients with treatment emergent adverse events(9 weeks)