Phase I Clinical Study to Compare and Evaluate the Pharmacokinetics and Safety of Orally Administered Vorolanib Tablets in Participants With Mild (Child-Pugh A) or Moderate (Child-Pugh B) Hepatic Impairment and Participants With Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum observed plasma concentration(Cmax)
研究概览
简要总结
This is a single-center, non-randomized, open-label, parallel-group, single-dose study designed to evaluate the safety and pharmacokinetic (PK) profile of vorolanib tablets in participants with hepatic impairment. A total of 24 participants (male and female) will be enrolled. Three study groups will be established, comprising participants with mild hepatic impairment (Child-Pugh A), moderate hepatic impairment (Child-Pugh B), and normal hepatic function, respectively. All participants will receive a single oral dose of 200 mg vorolanib tablets after a standard breakfast (regular meal) on Day 1 (D1). PK blood sampling and safety assessments will be performed at protocol-specified time points before and after drug administration for each participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
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
- •1. Voluntarily sign the informed consent form prior to initiation of any trial-related activities, understand the trial procedures and methods, and agree to complete the trial in strict accordance with the clinical trial protocol;
- •2. Trial participants (including their partners) agree not to conceive, donate sperm or oocytes from screening through 6 months after administration of the investigational product, and are willing to use highly effective contraceptive measures;
- •Trial participants with normal liver function must additionally meet all of the following criteria:
- •3. Meet the following demographic matching criteria at screening:
- •Weight-matched to the hepatic impairment group within ±10 kg of the mean value;
- •Age-matched to the hepatic impairment group within ±10 years of the mean value;
- •Sex-matched to the hepatic impairment group with a difference of ≤1 participant per sex;
- •Trial participants with hepatic impairment must additionally meet all of the following criteria:
- •4. Patients with hepatic insufficiency of Child-Pugh Class A or B and chronic liver injury caused by primary liver diseases (e.g., hepatitis B, hepatitis C, autoimmune hepatitis, alcoholic liver disease, etc.);
- •5. Clinically diagnosed cirrhosis.
排除标准
- •Trial participants with normal liver function will be excluded if they meet any of the following exclusion criteria:
- •1. A history of liver injury;
- •2. Presence of any clinically significant prior or current disease of the circulatory, endocrine, nervous, digestive, respiratory, hematologic, immunologic or psychiatric system, metabolic disorders, or any other disease that may interfere with trial results;
- •3. Abnormal findings on physical examination, vital signs, laboratory tests, 12-lead electrocardiogram or abdominal ultrasonography judged clinically significant by the investigator;
- •Trial participants with hepatic impairment will be excluded if they meet any of the following exclusion criteria:
- •4. The participant has any of the following conditions: acute liver injury of any etiology; history of liver transplantation; or cirrhosis complicated with the following complications deemed ineligible for enrollment by the investigator, including but not limited to liver failure, hepatic encephalopathy, hepatocellular carcinoma (except for Barcelona Clinic Liver Cancer Stage 0 or patients with curative treatment outcome), variceal bleeding of esophageal and gastric fundus occurring within 3 months prior to screening, confirmed hepatorenal or hepatopulmonary syndrome, and severe ascites or pleural effusion requiring puncture and drainage;
- •5. Any of the following laboratory findings at screening: (a) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >10×ULN; (b) absolute neutrophil count (NE#) <0.75×10⁹/L; (c) hemoglobin (HGB) <60 g/L; (d) alpha-fetoprotein (AFP) >100 ng/mL; (e) platelet count <40×10⁹/L.
研究组 & 干预措施
Participants with mild hepatic impairment (Child-Pugh A)
a single oral dose of 200 mg vorolanib tablets after a standard breakfast (regular meal) on Day 1
干预措施: vorolanib (Drug)
Participants with moderate hepatic impairment (Child-Pugh B)
a single oral dose of 200 mg vorolanib tablets after a standard breakfast (regular meal) on Day 1
干预措施: vorolanib (Drug)
Participants with normal hepatic function
a single oral dose of 200 mg vorolanib tablets after a standard breakfast (regular meal) on Day 1
干预措施: Vorolanib (Drug)
结局指标
主要结局
Maximum observed plasma concentration(Cmax)
时间窗: From pre-dose to 120 hours post-dose
Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC₀-t)
时间窗: From pre-dose to 120 hours post-dose
Area under the plasma concentration-time curve from time 0 to infinity (AUC₀-∞)
时间窗: From pre-dose to 120 hours post-dose
次要结局
未报告次要终点