An Open-Label, Paralleled Study of the Pharmacokinetics of HMS5552 Following a Single Oral Dose in Renal Impaired Subjects and Matched Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast
研究概览
简要总结
The objectives of this study is to access the pharmacokinetics and safety of HMS5552 in single dose in renal impaired subjects and matched healthy adult subjects.
详细描述
This is an open-label and paralleled study with single oral dose of HMS5552 given to renal impaired subjects and body index matched healthy volunteers.
The primary objective is to access the pharmacokinetic profiles of HMS5552 in 25 mg dose in renal impaired subjects and (gender, age and BMI) matched healthy adult subjects.
The secondary objective is to characterize the safety profiles of HMS5552 in single dose in renal impaired subjects.
The subjects include ESRD subjects without dialysis (P1 group), severe (P2 group), moderate (P3 group), mild (P4 group), and healthy subjects (H Group) matched with renal impairment subjects in gender, age and BMI. The number of subjects in each group was 6-8.
The study is divided into two parts:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For renal impaired subjects:
- •Male and female subjects between ages of 18 and 65 years, no less than 3 subjects in each gender.
- •Body weight≥50kg for male and ≥45kg for female； BMI: 18.5~30 kg/m2
- •eGFR: P1 < 15 mL/min/1.73 m2；P2: 15～29 mL/min/1.73 m2；P3: eGFR 30～59 mL/min/1.73 m2；P4: 60～89 mL/min/1.73 m2，and ACR≥ 3 mg/mmol；
- •Normal physical conditions, vital signs,12 lead ECG and laboratory recording, blood potassium 3.5~5.5mmol/L;
- •Left ventricular ejection fraction (LVEF) ≥50%
- •Willing to sign the informed consent form (ICF) and take reliable contraceptive measures within 6 months after taking the last dose of study drug;
- •Willing to adhere to the protocol requirement.
- •For healthy volunteers:
- •Male and female subjects between ages of 18 and 65 years, no less than 3 subjects in each gender.
- •Body weight≥50kg for male and ≥45kg for female； BMI: 18.5~30 kg/m2
- •MDRD eGFR: ≥90 mL/min/1.73 m2；
- •Gender, age (±5 years) and BMI (±15%) matched with corresponding subject in P1 group
- •Normal physical conditions, vital signs,12 lead ECG and laboratory recording
- •Systolic pressure: 90～140 mmHg，diastolic pressure:50～90 mmHg；
- •Willing to sign the informed consent form (ICF) and take reliable contraceptive measures within 6 months after taking the last dose of study drug;
- •Willing to adhere to the protocol requirement.
排除标准
- •Subjects with impaired renal function cannot be enrolled if they meet one of the following criteria:
- •Acute renal failure;
- •History of allergy;
- •In addition to renal impaired function, investigators adjudicate subjects have diseases that may affect drug absorption, distribution, metabolism or excretion;
- •Any other disease may receive treatment or surgery during the study
- •Abnormal of ECG performance or laboratory recording;
- •Family history of QT prolongation syndrome;
- •Have unstable cardiovascular disease, lung disease, gastrointestinal disease, liver disease, blood disease, mental disease, nervous system disease, immune deficiency disease or any malignant tumor;
- •History of cardiovascular and cerebrovascular disease;
- •Hear failure (NYHA) class III or IV;
- •Severe anemia, CHC<6.0g/dl at screening;
- •Severe infection, trauma, gastrointestinal operation or other surgery within 4 weeks before screening;
- •History of a) Type 1 diabetes, b) Acute complications of diabetes;
- •Serious hypoglycemia events within 3 months before screening;
- •More than 5 cigarettes per day within 3 months before screening;
- •Alcohol addicts;
- •History of drug abuse;
- •Healthy subjects cannot be enrolled if they meet one of the following criteria:
- •History of allergy;
- •Investigators adjudicate subjects have diseases that may affect drug absorption, distribution, metabolism or excretion;
- •Any other disease may receive treatment or surgery during the study
- •Abnormal of ECG performance or laboratory recording;
- •Family history of QT prolongation syndrome;
- •Have unstable cardiovascular disease, lung disease, gastrointestinal disease, liver disease, blood disease, mental disease, nervous system disease, immune deficiency disease or any malignant tumor; history of cardiovascular and cerebrovascular disease within 6 months before screening; severe infection, trauma, gastrointestinal operation or other surgery within 4 weeks before screening;
- •Anemia caused by any reason;
- •History of hypoglycemia (<3.9mmol/L);
- •More than 5 cigarettes per day within 3 months before screening;
- •Alcohol addicts;
- •History of drug abuse;
研究组 & 干预措施
Undialyzed ESRD subjects (P1)
Part 1: Undialyzed end stage renal disease (ESRD) patients to receive a single dose of HMS5552 ( 25mg ) tablets orally
.
干预措施: HMS5552 (Drug)
Healthy volunteers (H)
Part 1: Matched healthy volunteers to receive a single dose of HMS5552 ( 25mg ) tablets orally
Matching principle:
H group and P1 group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%
干预措施: HMS5552 (Drug)
Severe renal impaired subjects (P2)
Part 2：Severe renal impaired subjects to receive a single dose of HMS5552 ( 25mg ) tablets orally
Matching principle:
P2 group and H group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%
干预措施: HMS5552 (Drug)
Moderate renal impaired subjects (P3)
Part 2：Moderate renal impaired subjects to receive a single dose of HMS5552 ( 25mg ) tablets orally
Matching principle:
P3 group and H group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%
干预措施: HMS5552 (Drug)
Mild renal impaired subjects (P4)
Part 2：Mild renal impaired subjects to receive a single dose of HMS5552 ( 25mg ) tablets orally
Matching principle:
P4 group and H group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%
干预措施: HMS5552 (Drug)
结局指标
主要结局
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast
时间窗: Up to 72 hours post-dose
Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax
时间窗: Up to 72 hours post-dose
Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf
时间窗: Up to 72 hours post-dose
Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
次要结局
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of fu (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of T1/2 (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of CL/F (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf,u (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Tmax (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of CLr (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax,u (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast,u (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Vz/F (if applicable)(Up to 72 hours post-dose)
- The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Ae (if applicable)(Up to 72 hours post-dose)