A Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of Single and Multiple Dose of HRS-5965 Tablets in Healthy Subjects, and the Food Effect on Pharmacokinetics, and Pharmacokinetics in Subjects With Impaired Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- The incidence and severity of adverse events to assess safety and tolerability
研究概览
简要总结
The trial is the first human trial. The safety, tolerability, PK and PD of HRS-5965 tablets will be evaluated in healthy subjects and subjects with impaired renal function. The study was divided into three parts:
Part 1: single ascending dose, randomized, double-blind study，with 6 dose groups preset, of which 1 group will be administered under fasted and fed conditions; Part 2: Multiple ascending dose, randomized, double-blind study，with 4 dose groups preset; Part 3: an open-label, nonrandomized, single-dose study to evaluate the effect of severe renal impairment (RI) on the safety, tolerability, pharmacokinetics, and pharmacodynamics of HRS -5965 compared to demographically-matched healthy participants with normal renal function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects study
- •Healthy male or female, age ≥ 18 years old and ≤ 70 years old (on the day of signing the informed consent);
- •18.5kg/m2 ≤BMI<30 kg/m2, and the weight of men should be ≥ 50kg, and that of women should be ≥ 45kg.
- •Study on subjects with renal insufficiency
- •Age ≥ 18 years old and ≤ 70 years old (on the day of signing the informed consent), both men and women can;
- •18.5kg/m2≤BMI<30 kg/m2；
- •The estimated glomerular filtration rate of subjects with chronic renal insufficiency conforms to 15 ≤ EGFR < 30 ml/min/1.73m2 (calculated according to CKD-EPI formula, see Appendix 2 of the scheme).
排除标准
- •Healthy subjects study
- •The researcher has determined that there may be diseases or medical conditions that affect the absorption, distribution, metabolism and excretion of drugs or reduce compliance;
- •The estimated glomerular filtration rate conforms to EGFR < 90 ml/min/1.73m2 (calculated according to CKD-EPI formula, see Appendix 2 of the scheme);
- •According to the judgment of the researcher, any physiological or psychological disease or condition that may increase the risk of the test, affect the subject's compliance with the protocol, or affect the subject's completion of the test.
- •Study on subjects with renal insufficiency
- •Those who received renal replacement therapy within 12 weeks before screening; Or the two tests in the screening period indicate that the renal function is unstable (the results in the screening period meet the diagnostic criteria of 2012 KDIGO acute renal injury, or the changes that do not meet the above criteria but are judged to be clinically significant by the researcher. If there are reasonable reasons, the third test is allowed, and the interval between two consecutive tests should be more than 3 days but not more than 7 days);
- •According to the judgment of the researcher, the subject has any of the following: in the state of progression or prognosis of disease (including primary renal disease, complications and other complications); The treatment plan needs to be adjusted at any time; Any physical or mental disease or condition that may increase the risk of the test, affect the subject's compliance with the protocol, or affect the subject's completion of the test.
研究组 & 干预措施
Part 1
single ascending dose, randomized, double-blind study，with 6 dose groups preset, of which 1 group will be administered under fasted and fed conditions. The food impact study consisted of 10 subjects, 8 of whom received HRS-5965 tablets and 2 of whom received placebo. The remaining cohorts required 8 subjects each, with 6 receiving HRS-5965 tablets and 2 receiving placebo.
干预措施: HRS-5965 (Drug)
Part 1
single ascending dose, randomized, double-blind study，with 6 dose groups preset, of which 1 group will be administered under fasted and fed conditions. The food impact study consisted of 10 subjects, 8 of whom received HRS-5965 tablets and 2 of whom received placebo. The remaining cohorts required 8 subjects each, with 6 receiving HRS-5965 tablets and 2 receiving placebo.
干预措施: Placebo (Drug)
Part 2
Multiple ascending dose, randomized, double-blind study，with 4 dose groups preset; Each dose group consisted of 8 healthy adult subjects randomly assigned 6:2 to HRS-5965 tablets or placebo.
干预措施: HRS-5965 (Drug)
Part 2
Multiple ascending dose, randomized, double-blind study，with 4 dose groups preset; Each dose group consisted of 8 healthy adult subjects randomly assigned 6:2 to HRS-5965 tablets or placebo.
干预措施: Placebo (Drug)
Part 3
an open-label, nonrandomized, single-dose study to evaluate the effect of severe renal impairment (RI) on the safety, tolerability, pharmacokinetics, and pharmacodynamics of HRS -5965 compared to demographically-matched healthy participants with normal renal function. Subjects took HRS5965 tablets.
干预措施: HRS-5965 (Drug)
结局指标
主要结局
The incidence and severity of adverse events to assess safety and tolerability
时间窗: up to 24 days
次要结局
- Peak plasma concentration (Cmax) on Day 1 for Part 1 and Part 3(Pre-dose to 144 hours post-dose)
- Time to maximum plasma concentration (Tmax) on Day 1 and Day 10 for Part 2(Pre-dose to 144 hours post-dose)
- Peak plasma concentration (Cmax) on Day 1 and Day 10 for Part 2(Pre-dose to 144 hours post-dose)
- Area under the plasma concentration versus time curve (AUC) on Day 1 for Part 1 and Part 3(Pre-dose to 144 hours post-dose)
- • Area under the plasma concentration versus time curve (AUC) on Day 1 and Day 10 for Part 2(Pre-dose to 144 hours post-dose)
- Time to maximum plasma concentration (Tmax) on Day 1 for Part 1 and Part 3(Pre-dose to 144 hours post-dose)