A Randomised, Double-blind, Three-period, Partially Replicated Crossover, Euglycaemic Glucose Clamp Study in Healthy Volunteers to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity of Biocon's Human Insulin R U-500 and Humulin® R U-500 (RHINE-4: Recombinant Human INsulin Equivalence-4)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 2
- 主要终点
- Primary pharmacokinetics (PK) endpoint: maximum observed insulin concentration(Cins.max)
研究概览
简要总结
Single-centre, randomised, double-blind, three-period, six-sequence, partially replicated design, crossover trial in healthy subjects
详细描述
The present study is designed to demonstrate pharmacokinetic and pharmacodynamic equivalence of Biocon's Human Insulin R U-500 with Humulin® R U-500 in healthy subjects.
The treatment consists of one single dose of the test or reference product, administered during each of the three study periods, separated by 5-7 days between each dosing. The planned trial duration for each subject is about 18 to 44 days. Eligible subjects will undergo three euglycaemic clamp examinations (each of 24 hours duration).
Depending on the sequence in which a particular subject is randomized, each subject will either undergo two clamps with administration of test product plus one clamp with administration of reference product, or, two clamps with administration of reference product plus one clamp with administration of test product, in random order.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or post-menopausal female subjects. The post-menopausal state is defined as no menses for 12 months without an alternative medical cause and confirmed by a follicle stimulating hormone (FSH) level in the post-menopausal range (≥ 25.8 IU/L).
- •Age between 18 and 55 years, both inclusive.
- •Body Mass Index (BMI) between 18.5 and 29.0 kg/m2, both inclusive.
- •Fasting plasma glucose concentration ≤ 100 mg/dL.
- •Considered generally healthy upon completing the medical history and screening safety assessments, as judged by the Investigator.
排除标准
- •Known or suspected hypersensitivity to investigational medicinal products (IMPs) or related products.
- •Receipt of any medicinal product in clinical development within 30 days or five times its half-life (whichever is longer) before randomisation in this trial.
- •Systolic blood pressure < 90 mmHg or > 139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 mmHg after resting for at least 5 minutes in the supine position (excluding white-coat hypertension; therefore, a repeat test showing results within range will be acceptable).
- •Pulse rate at rest outside the range of 50-90 beats per minute.
结局指标
主要结局
Primary pharmacokinetics (PK) endpoint: maximum observed insulin concentration(Cins.max)
时间窗: NAP (Not Applicable)
Maximum observed insulin concentration
Primary pharmacodynamics (PD) endpoint:maximum observed glucose infusion rate (GIRmax)
时间窗: NAP (Not Applicable)
Maximum observed glucose infusion rate
Primary pharmacokinetics (PK) endpoint: area under the insulin concentration curve(AUCins).0-12h
时间窗: 0 to12 hours
Area under the insulin concentration curve
Primary pharmacodynamics (PD) endpoint:area under the glucose infusion rate curve (AUCGIR)0-12h
时间窗: 0 to 12 hours
Area under the glucose infusion rate curve
次要结局
- Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-24h(0 to 24 hours)
- Secondary pharmacokinetics (PK) endpoint: time(t)50%-Insulin (INS)(early)(0 to 24 hours)
- Secondary pharmacodynamics (PD) endpoint:time to half-maximum glucose infusion rate before GIRmax (tGIR.50%-early)(0 to 24 hours)
- Secondary pharmacodynamics (PD) endpoint: Onset of action, time from trial product administration until plasma glucose concentration has decreased at least 5 mg/dL from baseline,(0 to 24 hours)
- Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve(AUCins).0-infinity(0 hours to 24 hours)
- Secondary pharmacokinetics (PK) endpoint: area under the insulin concentration-time curve (AUCins).12-24h(12 to 24 hours)
- Secondary pharmacodynamics (PD) endpoint: time to half-maximum glucose infusion rate after GIRmax (tGIR.50%-late)(0 to 24 hours)
- Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).0-24h(0 to 24 hours)
- Secondary pharmacokinetics (PK) endpoint:time to maximum observed insulin concentration (tmax.ins)(0 to 24 hours)
- Secondary pharmacokinetics (PK) endpoint:terminal elimination rate constant of insulin (λz)(0 to 24 hours)
- Secondary pharmacokinetics (PK) endpoint: terminal elimination half-life (t½)(0 to 24 hours)
- Secondary pharmacokinetics (PK) endpoint: time(t) 50%-Insulin (INS)(late)(0 to 24 hours)
- Secondary pharmacodynamics (PD) endpoint: areas under the glucose infusion rate curve(AUCGIR).12-24h(12 to 24 hours)
- Secondary pharmacodynamics (PD) endpoint: time to maximum glucose infusion rate(tmax.GIR)(0 to 24 hours)