How olverembatinib is processed in people with liver impairment

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

This test gives a single 20 mg dose of olverembatinib to people with different levels of chronic liver impairment and matched healthy volunteers to see how the drug is absorbed, distributed, metabolized, and cleared.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (Industry-sponsored)
• Drugs / interventions: olverembatinib
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07282093 on ClinicalTrials.gov

What this trial studies

This is a non-randomized, open-label, parallel single-dose pharmacokinetic study comparing participants with mild (Child-Pugh A), moderate (Child-Pugh B), and severe (Child-Pugh C) hepatic impairment to sex-, age-, and body weight-matched healthy volunteers. Each participant receives a single 20 mg oral dose of olverembatinib and undergoes timed blood sampling and safety monitoring to measure drug concentrations and standard tolerability parameters. The PK parameters (for example, Cmax, AUC, half-life, and clearance) will be compared across groups to characterize the effect of hepatic impairment on drug exposure. Results will be used to inform dosing recommendations for patients with impaired liver function.

Who should consider this trial

Good fit: Adults with chronic hepatic impairment classified as Child-Pugh A, B, or C who meet BMI, weight, and safety screening criteria, as well as matched healthy volunteers, are the intended participants.

Not a fit: Patients seeking therapeutic benefit for a medical condition should not expect clinical benefit from this single-dose PK study, and those with acute liver failure, unstable medical illness, pregnancy, breastfeeding, or outside the BMI/weight limits are unlikely to qualify or benefit.

Why it matters

Potential benefit: If successful, the study could define safe dose adjustments for olverembatinib in people with liver impairment to reduce the risk of toxicity or underdosing.

How similar studies have performed: PK studies of other tyrosine kinase inhibitors in hepatic impairment have been successfully used to guide dose adjustments, so the approach is standard even if olverembatinib-specific data are limited.

Eligibility criteria

Inclusion Criteria:

1. The participant voluntarily joins the study, signs the Informed Consent Form, and demonstrates good compliance.
2. Body Mass Index (BMI) between 18 and 30 kg/m² (inclusive), with male weight ≥ 50 kg and female weight ≥ 45 kg.
3. 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.
4. 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.
5. 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. 3. 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.

Exclusion Criteria:

1. Drug-induced liver injury.
2. 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.
3. History of cholestasis, biliary tract infection, or other diseases affecting bile excretion within 3 months prior to screening.
4. 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.
5. History of significant allergy or intolerance to any drug, food, or other substance.
6. 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.
7. 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.
8. 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.
9. 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.
10. Use of systemic medications with known potential hepatotoxicity for 7 consecutive days or more within 14 days prior to study drug administration.
11. Use of traditional Chinese medicine (herbal medicines, proprietary Chinese medicines), dietary supplements, or vitamins within 14 days prior to study drug administration.
12. 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.
13. Positive urine drug screen or alcohol breath test at screening.
14. 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.
15. 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.
16. 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.
17. Blood donation (or blood loss) ≥ 400 mL, or receipt of blood transfusion or blood products within 3 months prior to screening.
18. History of needle or blood phobia, difficulty with blood collection, or intolerance to venipuncture.
19. 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.
20. Additional Criteria for Participants with Normal Hepatic Function Only:

1). 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.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Suzhou Medical University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Principal investigator: Liyan Miao, M.D.,Ph.D. — M.D.,Ph.D.
• Study coordinator: Yifan Zhai, M.D., Ph.D.

Conditions Pharmacokinetic; Olverembatinib; olverembatinib