A Randomized, Double-blind, Placebo-controlled, Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and the Impact of Food on Pharmacokinetics of HS-10398 in Healthy Participants, and a Clinical Trial to Assess the Pharmacokinetic Characteristics of HS-10398 in Participants With Kidney Dysfunction
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 116
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events (AEs)
研究概览
简要总结
A randomized, double-blind, placebo-controlled, dose-escalation clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics, and the impact of food on pharmacokinetics of oral HS-10398 in Chinese healthy participants, and a clinical trial to assess the pharmacokinetic characteristics of oral HS-10398 in Chinese participants with kidney dysfunction
详细描述
This is a phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation clinical trial. The primary objective is to evaluate the safety, tolerability, and pharmacokinetic characteristics of single and multiple oral doses of HS-10398 in Chinese healthy participants. The secondary objective is to assess the impact of food on the pharmacokinetics of single oral doses of HS-10398 in Chinese healthy participants, as well as to evaluate the pharmacokinetic characteristics of oral HS-10398 in Chinese participants with kidney dysfunction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- 是
入选标准
- •Healthy participants aged from 18 to 64 years
- •Subjects need to fully understand the research content and process, as well as possible adverse reactions, and voluntarily signed Informed Consent Form
- •Males' weight should be ≥ 50kg, and females' weight should be ≥ 45kg. Body mass index (BMI), calculated as weight/height^2 (kg/m^2), should be controlled within the range of 19 to 28, including the critical value
- •Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration
- •Participants with Kidney Dysfunction must have met the following additional criteria to be enrolled in this study：Patients with chronic kidney disease (defined as the presence of any markers of kidney damage or an estimated glomerular filtration rate (eGFR) persistently less than 90 mL/min/1.73m² for more than 3 months), and with an estimated glomerular filtration rate (eGFR) at screening and baseline assessments (with a minimum interval of 3 days between screening and baseline assessments) meeting the criteria of 60≤eGFR<90 mL/min/1.73m².
排除标准
- •Has a history of chronic or serious disease from neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, metabolic endocrine system, skin disease, blood system, immune system or tumor
- •Has taken any drugs, including prescription drugs, over-the-counter drugs, herbal preparations, some health products or inhibitor/inducer of CYP3A4/5 or CYP2C8 or any medications that inhibit P-glycoprotein transporters., within 2 weeks (or 5 half-lives) before screening and throughout the study period
- •Has clinically significant ECG abnormalities, such as QT interval corrected according to Fridericia formula(QTcF), >450 ms (males), >470 ms (females)
- •Has participated in another clinical trial involving drugs or medical devices within the month prior to screening and received investigational drugs or used medical devices, or within 5 half-lives of the investigational drugs from another trial at the time of screening, whichever is longer
- •Unable to abstain from smoking and alcohol.
- •History of drug dependence or substance abuse
研究组 & 干预措施
Cohort1：HS-10398
SAD： HS-10398 capsule
干预措施: HS-10398 (Drug)
Cohort2：HS-10398 Placebo
SAD：HS-10398 capsule placebo
干预措施: HS-10398 Placebo (Drug)
Cohort3：HS-10398
MAD： HS-10398 capsule
干预措施: HS-10398 (Drug)
Cohort4：HS-10398 Placebo
MAD：HS-10398 capsule placebo
干预措施: HS-10398 Placebo (Drug)
Cohort5：HS-10398
HS-10398 capsule will be administered orally once on Day 1 in Participants With Kidney Dysfunction
干预措施: HS-10398 (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs)
时间窗: From screening to day 15
The definition of adverse event \[AE\] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Serious adverse events (SAEs)
时间窗: From screening to day 15
The definition of serious adverse event \[SAE\] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.
次要结局
- Elimination Halflife (T1/2)(up to 216 hours after dosing)
- Observed maximum plasma concentration (Cmax)(up to 216 hours after dosing)
- Apparent clearance（CL/F）(up to 216 hours after dosing)
- Time to reach maximum plasma concentration (Tmax)(up to 216 hours after dosing)
- Apparent Volume of Distribution（Vd/F）(up to 216 hours after dosing)