An Open-label, Single-dose Study to Assess the Pharmacokinetics of HSK7653 Tablets in Subjects With Varying Degrees of Renal Impairment Compared to the Control Subjects With Normal Renal Function

Haisco Pharmaceutical Group Co., Ltd.1 个研究点分布在 1 个国家目标入组 42 人开始时间: 2022年8月4日最近更新: 2023年1月3日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 42
试验地点: 1
主要终点: Cmax

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is an open-label, single-dose study to evaluate the pharmacokinetics, pharmacodynamics and safety of HSK7653 in subjects with mild, moderate, severe renal impairment and subjects with kidney failure compared to the matched control subjects with normal renal function.

详细描述

This is an open-label, single-dose Phase I study that evaluate the pharmacokinetics, pharmacodynamics and safety of a single dose of HSK7653 10 mg in subjects with mild, moderate, and severe renal impairment , subjects with kidney failure and the control subjects with normal renal function. This study consists of a screening period (Day -14 to Day -1), a baseline period (Day -1), a treatment period (Day 1 to Day 29), and a follow-up call on Day 32.

Subjects will be enrolled in the following groups:

Glomerular filtration rate (GFR, unit mL/min/1.73m^2) will be calculated based on Modification of Diet in Renal Disease (MDRD) equation at screening, Multiply it by BSA, then divide by 1.73 to convert to absolute GFR (unit, mL/min) (group A1) mild renal impairment (60 ≤ GFR< 90 mL/min); (group B1) moderate renal impairment (30 ≤ GFR<60 mL/min); (group C1) severe renal impairment (15 ≤ GFR< 30 mL/min); (group D1) kidney failure (<15 mL/min, not on hemodialysis); (group A2,B2,C2,D2) control subjects with normal renal function will be matched with subjects with renal impairment by weight, age, and sex (GFR≥90 mL/min).If subjects in group A2 can be matched with the subjects in groups A1 and B1 at the same time, the subjects in group B2 will not be enrolled, and so on.

Approximately 64 subjects will be enrolled in total.

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 79 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•Subjects with renal impairment(RI):
•Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
•18 years to 79 years (inclusive), male and female;
•Male subjects weight ≥50 kg and female subjects weight ≥45 kg. Body mass index (BMI) : 18-30 kg/m2 (inclusive) (BMI= weight (kg)/height2 (m^2));
•Subjects with medically stable RI until study completion corresponding to the Classifications of Renal Function based on GFR: mild RI: 60≤GFR<90 mL/min; moderate RI: 30≤GFR<60 mL/min, severe RI:15≤GFR<30 mL/min, kidney failure:GFR<15 mL/min (not on hemodialysis);
•Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests (hematology, serum chemistry, coagulation and urinalysis test) results were deemed appropriate by the investigator;
•Not in use of any drug within 2 weeks prior to screening, except for the medication necessary for RI/ other comorbidities (last more than four weeks in good compliance);
•Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration;
•Subjects with normal renal function :
•Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
•18 years to 79 years (inclusive), male and female, age and sex must be matched with subjects with RI;
•Male subjects weight ≥50 kg and female subjects weight ≥45 kg, weight must be matched with subjects with RI. Body mass index (BMI) : 18-30 kg/m^2 (inclusive) (BMI= weight (kg)/height2 (m^2));
•90≤GFR<130 mL/min;
•Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests (hematology, serum chemistry, coagulation and urinalysis test) results were deemed appropriate by the investigator;
•Not in use of any drug within 2 weeks prior to screening, except for the medication necessary for comorbidities (last more than four weeks in good compliance);
•Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration；

排除标准

•Subjects who have a allergic history of DPP4 inhibitors or have a history of allergy to the test drug and the related compounds;
•Have a history of severe and uncontrolled diseases, such as cardiovascular, respiratory, liver, gastrointestinal, endocrine, hematologic, mental/nervous systems diseases within one year prior to screening；
•History or clinical evidence of acute or chronic pancreatitis, or clinically significant abnormalities in blood lipase and/or blood amylase results at screening;
•Have conditions that may affect drug absorption, distribution, metabolism, or excretion (e.g., disease, drugs or surgery);
•Use of any DPP-IV enzyme inhibitor within 2 weeks prior to the screening;
•Experienced severe hypoglycemia within 3 months before screening;
•Acute renal failure;
•Smoking more than 5 cigarettes per day within 3 months prior to screening or smoking during the study；
•Average alcohol intake is more than 14 unit per week (1unit=17.7 mL alcohol , 1 unit=357mL 5% alcohol beer, or 43mL 40% alcohol spirit, or 147mL 12% alcohol wine) within the 3 months prior to screening, or taking any alcohol during study or a positive ethanol breath test at screening;
•Drug abuse history within 5 years prior to screening, or positive urine drug screen at screening；
•History of high consumption of grapefruit juice, methylxanthine-rich food or beverage (such as coffee, tea, cola, chocolate, energy drinks) , consumption of grapefruit juice, methylxanthine-rich food within 48 hours before the administration ；
•Participation in another clinical trial within 3 months before screening；
•Blood donation (or blood loss) ≥400 mL, or receiving blood products to improve anemia within 3 months prior to the screening；
•Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2 × upper limit of normal, or bilirubin > 1.5 × upper limit of normal；
•Have a positive result for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or anti-treponema pallidum specific antibody；
•A pregnant/lactating woman, or has a positive pregnancy test at screening or during the trial；
•Not suitable for this study as judged by the investigator.