An Open-Label, Phase 1 Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics of Olverembatinib

Ascentage Pharma Group Inc.1 个研究点分布在 1 个国家目标入组 48 人开始时间: 2025年11月11日最近更新: 2025年12月23日

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: Ascentage Pharma Group Inc.
入组人数: 48
试验地点: 1
主要终点: Apparent Clearance (CL/F)

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 a non-randomized, open-label, parallel, single-dose study to evaluate the pharmacokinetic profile of olverembatinib in participants with normal or impaired liver function.

详细描述

To evaluate the PK characteristics of olverembatinib in participants with mild hepatic impairment (Child-Pugh Class A), moderate hepatic impairment (Child-Pugh Class B), severe hepatic impairment (Child-Pugh Class C) and sex, age, and body weight-matched healthy participants with normal hepatic function, so as to provide a scientific basis for the appropriate dose and/or dosing interval adjustment in participants with hepatic impairment.

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

入选标准

•The participant voluntarily joins the study, signs the Informed Consent Form, and demonstrates good compliance.
•Body Mass Index (BMI) between 18 and 30 kg/m² (inclusive), with male weight ≥ 50 kg and female weight ≥ 45 kg.
•The investigator judges the participant suitable to participate in this study based on physical examination, vital signs, laboratory tests, and 12-lead electrocardiogram (ECG) examination.
•Female participants of childbearing potential must agree to use effective contraception during the study and for 3 months after the study ends; must have a negative serum pregnancy test within 7 days prior to study enrollment; and must not be breastfeeding. Male participants must agree to use effective contraception during the study and for 3 months after the study ends.
•Additional Criteria for Participants with hepatic impairment Only:
•1. Chronic hepatic impairment due to viral hepatitis, alcoholic liver disease, autoimmune hepatitis, or other causes.
•2. Hepatic impairment classified as Child-Pugh Class A, B, or C.
•Coagulation function: INR ≤ 2.5 without intervention with procoagulant drugs (after a 2-week washout period). Hematology: Neutrophils ≥ 1.0 × 10⁹/L, Hemoglobin ≥ 70 g/L, Platelets ≥ 30 × 10⁹/L. Liver function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 5 times the Upper Limit of Normal (ULN); Total Bilirubin ≤ 5 × ULN.
•4. Stable treatment for hepatic impairment, complications, and other concomitant diseases prior to study drug administration, with no need for dosage adjustment. Treatment for hepatic impairment must have been stable for at least 4 weeks.

排除标准

•Drug-induced liver injury.
•Any of the following conditions: history of liver transplantation; presence of acute or worsening liver injury due to any cause; liver failure; concurrent Grade 3/4 hepatic encephalopathy; active hepatocellular carcinoma lesions; severe esophageal or gastric varices or history of rupture and bleeding; severe/late-stage ascites or pleural effusion requiring paracentesis/thoracentesis and albumin supplementation; hepatorenal syndrome; or any other condition deemed by the investigator as unsuitable for study participation.
•History of cholestasis, biliary tract infection, or other diseases affecting bile excretion within 3 months prior to screening.
•Esophageal or gastric variceal bleeding due to portal hypertension within 3 months prior to screening, or history of portosystemic shunt surgery (including Transjugular Intrahepatic Portosystemic Shunt - TIPS) within 6 months prior to screening.
•History of significant allergy or intolerance to any drug, food, or other substance.
•History of any clinically significant disease in the neurological, cardiovascular, digestive, respiratory, urinary, endocrine, hematological, immune systems, or any other disease or condition that the investigator believes may affect the trial results.
•History of surgery that may affect drug absorption, distribution, metabolism, or excretion, or plans for surgery or other reasons requiring hospitalization during the expected study period.
•Uncontrolled bacterial, viral, parasitic, or fungal infection requiring treatment at the time of screening (except Hepatitis B), or history of severe active infection within 1 month prior to screening.
•Positive Human Immunodeficiency Virus (HIV) antigen/antibody test at screening. For participants with normal hepatic function: Positive Treponema pallidum antibody. For hepatically impaired participants: Active syphilis.
•Use of systemic medications with known potential hepatotoxicity for 7 consecutive days or more within 14 days prior to study drug administration.
•Use of traditional Chinese medicine (herbal medicines, proprietary Chinese medicines), dietary supplements, or vitamins within 14 days prior to study drug administration.
•Systemic use of moderate or potent CYP3A4 inhibitors (e.g., itraconazole, fluconazole) or moderate or potent CYP3A4 inducers within 14 days prior to study drug administration.
•Positive urine drug screen or alcohol breath test at screening.
•Excessive alcohol intake (averaging more than 14 units of alcohol per week) within 3 months prior to screening, or inability to abstain from alcohol during the trial period.
•Consumption of grapefruit/juice, foods or beverages rich in methylxanthines, engagement in strenuous exercise, or presence of other factors affecting drug absorption, distribution, metabolism, or excretion within 7 days prior to study drug administration, and inability to abstain from these during the hospitalization period.
•Participation in other investigational drug or medical device clinical trials within 3 months prior to the first dose of the study drug, or participation in 3 or more drug or medical device clinical trials within the past year. If the half-life of the other investigational drug is long, a longer interval is required, at least 5 times the half-life of that drug.
•Blood donation (or blood loss) ≥ 400 mL, or receipt of blood transfusion or blood products within 3 months prior to screening.
•History of needle or blood phobia, difficulty with blood collection, or intolerance to venipuncture.
•Unwillingness or inability to comply with the study procedures outlined in the protocol, or any other reason considered by the investigator as unsuitable for participation in this clinical study.
•Additional Criteria for Participants with Normal Hepatic Function Only:
•. For participants with normal hepatic function: History of hepatitis, Hepatitis B, or Hepatitis C. History of hepatic impairment, or findings during screening physical examination or laboratory tests suggesting existing or potential hepatic impairment; Positive Hepatitis B Surface Antigen (HBsAg) or positive anti-HCV antibody.