DZD9008 PK Study in Hepatic Impairment Subjects

Exclusion Criteria

• •1. The subject has a history or clinical manifestations of a significant neurological, renal, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, or psychiatric disease that would preclude study participation, as judged by the investigator.
• •2. The subject has any surgical or medical condition that may alter the absorption, distribution, metabolism, or excretion of drugs (e.g., gastrectomy).
• •3. The subject has a history of cancer (malignancy) with the following exceptions:
• •1. adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix, or
• •2. other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study
• •4. The subject has a history of being immunocompromised or has a positive test result for HIV types 1 or 2 antibodies at screening.
• •5. The subject has an acute or chronic infection requiring treatment with oral antibiotics (except, rifaximin for the treatment of hepatic encephalopathy), antivirals, antiparasitic, antiprotozoals, or antifungals within 4 weeks prior to Day 1 or superficial skin infection within 1 week prior to Day 1.
• •6. The subject has a history of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of long QT syndrome), has clinically significant hypokalemia or hypomagnesemia, and is taking concomitant medications that prolong the QT/QTc interval.
• •7. The subject has uncontrolled hypertension despite optimal medical management.
• •8. The subject had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study drug administration.
• •9. The subject tests positive for breath alcohol test at screening and on check-in (Day 1).
• •10. The subject is unable or unwilling to restrict smoking to 5 cigarettes or less per day.
• •11. The subject is involved in strenuous activity or contact sports within 24 hours of the first dose of study drug or during the study.
• •12. The subject has donated blood (excluding plasma donation) of ≥ 500 mL within 60 days before the first dose of study drug.
• •13. The subject has poor peripheral venous access.
• •14. The subject should not be any of the following:
• •1. investigator staff member or their family members
• •2. site staff member otherwise supervised by the investigator, or employees, including their family members, directly involved in the conduct of the study
• •15. The subject has a history of relevant drug and/or food allergies (ie, allergy to DZD9008 or any excipients, or any significant food allergy).
• •16. The subject has received DZD9008 or any other investigational drug in another investigational study within 30 days of dosing.
• •17. The subject is enrolled in another clinical study or has used any investigational drug or device within 4 weeks (or 5 times the half-life of the pervious drug \[if known\], whichever is longer), prior to dosing with study drug. The window will be derived from the date of the last dose of study drug in the previous study.
• •18. The subject has used a strong or moderate inhibitor or inducer of CYP3A4 and/or P gp including St. John's Wort, within 14 days and 28 days, respectively, prior to dosing and until the completion of the last PK sample collection unless it is deemed acceptable following consultation with Dizal Pharma's medical monitor and the investigator.
• •19. The subject has used PPIs within 5 days prior to dosing until 24 hours after dosing. Use of H2-antagonists and antacids within 12 hours prior to dosing until 12 hours after dosing unless it is deemed acceptable following consultation with Dizal Pharma's medical monitor and the investigator.
• •20. In the opinion of the investigator, the subject is not suitable for entry into the study.
• •21. The subject with normal hepatic function has any of the following:
• •1. evidence or history of bleeding diathesis, or
• •2. any hemorrhage or moderate bleeding event within 4 weeks of start of study drug administration
• •22. The subject has a positive result for HBsAg or HCV Ab.
• •23. The subject has an estimated glomerular filtration rate (CKD-EPI formula or Cockcroft-Gault method) of \< 90 mL/min.
• •24. The subject has used any vaccine or used any prescription (excluding hormonal birth control and hormone replacement therapy) or over the counter medications (except paracetamol \[up to 2 g per day\]), including herbal or nutritional supplements, within 14 days before the first dose of study drug and throughout the study.
• •25. The subject has a positive test result for drugs of abuse or alcohol at screening or before the first dose of study drug.
• •26. The subject has fluctuating or rapidly deteriorating hepatic function, as indicated by recent history or worsening of clinical (ie, abdominal pain, nausea, vomiting, anorexia, or fever) and/or laboratory signs of hepatic impairment, as judged by the investigator.
• •27. The subject has evidence of acute viral hepatitis within 30 days before dosing with study drug.
• •28. The subject has an active hepatitis B or C viral infection.
• •29. The subject has history or symptoms of hepatic encephalopathy Grade 2 or above within 3 months prior to screening visit.
• •30. The subject has a history of unstable diabetes mellitus as evidenced by HbA1c ≥ 9% at screening.
• •31. In the opinion of the investigator, the subject has clinically demonstrable severe ascites and/or pleural effusion.
• •32. The subject has evidence of hepatopulmonary syndrome, hydrothorax, or hepatorenal syndrome.
• •33. The subject had an organ transplant or is on a waiting list.
• •34. The subject had a portosystemic shunt (including transjugular intrahepatic portosystemic shunts).
• •35. The subject has an estimated glomerular filtration rate (CKD-EPI formula) of \< 60 mL/min.
• •36. The subject has symptoms consistent with spontaneous bacterial peritonitis, known active spontaneous bacterial peritonitis, or a history of spontaneous peritonitis within the last 6 months.
• •37. The subject is suspected of having hepatocellular carcinoma (ie, if α fetoprotein \> 50 ng/mL at screening), subjects will undergo appropriate diagnostic studies (e.g., CT scan or hepatic ultrasound) to exclude the possibility of hepatocellular carcinoma.
• •38. The subject has received any vaccine or used any prescription (excluding hormonal birth control and hormone replacement therapy) or over the counter medications, including herbal or nutritional supplements, within 14 days before the first dose of study drug and throughout the study, except those essential for the management of hepatic impairment or the treatment of stable concomitant medical conditions, as judged by the investigator. The dose of an approved medication must remain stable from 7 days before study drug dosing and throughout the study.
• •39. The subject has a positive test result for drugs of abuse (except positive test results associated with prescription medications that have been reviewed and approved by the investigator) or alcohol at screening or prior to study drug dosing.