A Study to Investigate the Pharmacokinetics of JMKX003142 in Healthy Participants and Participants With Hepatic Impairment

Prior treatment

• Participant with severe active infection, gastrointestinal surgery, or other major surgery within 4 weeks prior to screening.
• Participant who donated or loss blood ≥400 mL within 3 months prior to screening, or who received blood transfusions or blood products.
• Participant who administered any study drug within 3 months prior to screening, or who are currently participating in another clinical trial.
• Participant who smoked \>5 cigarettes per day within the 3 months prior to screening, or who are unable to commit to abstaining from smoking/tobacco products during the trial, or who have a positive nicotine screening test.
• History of alcoholism or heavy alcohol consumption within 6 months prior to screening \[\>14 units of alcohol per week: 1 unit ≈ 10 mL of pure alcohol, equivalent to approximately 285 mL of beer (3.5% ABV), 25 mL of spirits (40% ABV), or 100 mL of wine (10% ABV)\]; or inability to abstain from alcohol during the trial; or a positive breath alcohol test.
• Consumption of grapefruit juice or methylxanthine-rich foods or beverages (e.g., coffee, tea, cola, chocolate, energy drinks) within 3 days prior to dosing, or Engagement in strenuous exercise or other factors that may affect drug absorption, distribution, metabolism, or excretion.
• Use of any medication (including prescription drugs, over-the-counter drugs, traditional Chinese medicine, vitamins, or dietary supplements) within 14 days prior to dosing (or 5 half-lives, whichever is longer); except for stable medication use in subjects with hepatic impairment.
• Use of any drug that inhibits or induces the activity of hepatic drug-metabolizing enzymes within 14 days prior to screening (see Appendix 5, Section 10.5 for details.
• History of drug-induced liver injury (DILI) or prior liver transplantation.
• Acute liver injury due to any cause within 3 months prior to screening.
• History of cholestatic liver disease or biliary obstruction, or other conditions affecting bile excretion, within 3 months prior to screening.
• History of portal hypertension complicated by esophagogastric variceal bleeding within 6 months prior to screening, or portosystemic shunt surgery, including transjugular intrahepatic portosystemic shunt (TIPS), within 6 months prior to screening.

Other illness

• Allergy to the active ingredients and excipients of JMKX003142, or a history of allergy to two or more substances.
• Participant with clinically significant diseases, including but not limited to: circulatory, respiratory, digestive, urinary and reproductive, endocrine, nervous, and other relevant systems, or diseases or conditions that the investigator considers may affect the study results (except for participant who had impaired liver function and its complications).
• Effect of drug absorption (e.g., dysphagia, gastrointestinal resection, ulcerative colitis, symptomatic or inflammatory bowel disease, chronic diarrhea, and intestinal obstruction, among other gastrointestinal diseases).
• Participant with a history of Hemophobia and Fear of needles, unable to draw blood.
• History of drug dependence/abuse, or a positive drug screen.
• Positive human immunodeficiency virus (HIV) antibody or positive syphilis screening test.
• Any other condition that, in the investigator's opinion, would make the subject unsuitable for participation in this study.
  • Participants with Normal Hepatic Function Only:
• Positive hepatitis B surface antigen (HBsAg) or positive hepatitis C virus (HCV) antibody test.
  • Hepatically-Impaired Participants Only :
• Hepatic failure, or complications hepatic encephalopathy or esophagogastric variceal bleeding that, in the investigator's opinion, are unsuitable for participation in this study.

Lab values

• Clinically significant ECG abnormalities at screening, including tachycardia or bradycardia requiring pharmacological treatment, second- or third-degree atrioventricular block, or prolonged QTcF interval (corrected by Fridericia's formula, QTcF = QT/RR\^(1/3), rounded to the nearest integer) (male QTcF \> 450 ms, female QTcF \> 470 ms); or other abnormalities deemed clinically significant by the investigator.
• History of hepatic impairment, or physical examination and laboratory tests at screening indicating the presence or possible presence of hepatic impairment.
• Severe or late-stage ascites or pleural effusion requiring paracentesis and albumin supplementation, or hepatorenal syndrome.
• Major Organ Function:
  • Coagulation function: INR \> 2.5 without intervention by procoagulant or anticoagulant medications (after a 2-week washout period).
  • Hematology: absolute neutrophil count (ANC) \< 0.75 × 10⁹/L, hemoglobin \< 80 g/L, and platelet count \< 30 × 10⁹/L.
  • Hepatic function: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 5 × upper limit of normal (ULN).
  • Renal function: estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m², calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Other

• All Participants:

• All Participants:
• The participant is able to understand the content of this trial and is willing to comply with the policies, procedures, and constraints of the study, and a written informed consent form must be signed by the subject or a legally authorized representative before any study procedure is performed.
• At the time of signing the informed consent form, aged 18 to 75 years (inclusive), with body weight ≥50 kg for males or ≥45 kg for females, and body mass index (BMI) 18.0 to 30.0 kg/m² (inclusive).
• At screening, all examinations (including physical examination, vital signs, complete blood count, urinalysis, blood biochemistry, coagulation function, electrocardiogram, chest X-ray, abdominal ultrasonography, etc.) were judged by the investigator to be suitable for participation in this study.
• Female participants of childbearing potential with a negative pregnancy test result during the screening period or who are non-lactating; participants of childbearing potential with no plans for conception, cryopreservation, or donation of sperm or ova from the time of informed consent signing until 3 months after the last dose, and who agree to use effective contraception.
  • Hepatically-Impaired Participants Only :
• Participant with chronic hepatic impairment due to viral hepatitis, alcoholic liver disease, autoimmune hepatitis, or other primary liver diseases.
• Classified as Child-Pugh class A (score 5-6, cohort 1) or class B (score 7-9, cohort 2) by the Child-Pugh scoring system at screening, and had not received albumin within 14 days prior to screening.
• Participant with documented stable hepatic impairment (for ≥1 month) based on medical history, physical examination, laboratory testing, or imaging, who either have not taken any medication within 2 weeks prior to screening or, if long-term treatment is required for hepatic impairment and/or concomitant diseases, have had stable medication for at least 4 weeks prior to initiation of the study drug (stable medication to be determined by the investigator, excluding medications prohibited by the protocol).