| Eligibility |
Inclusion Criteria:
- 1. Fully understand the content, process and possible adverse reactions of the trial
before the trial, and be able to complete the study and sign the informed consent
according to the requirements of the trial protocol;
2. Adults of both sexes aged from 18 to 70 years old (both ends, based on written
informed consent);
3. The body weight of male subjects should not be less than 50 kg and the body weight
of female subjects should not be less than 45 kg. Body mass index (BMI) : 19-32 kg/m2
(including cut-off value);
4. chronic stable liver impairment (no clinically significant change in disease status
as judged by the investigator to have occurred for at least 28 days (or up to 14 days
for patients with moderate liver function) before taking the study drug) due to
primary liver disease (e.g., autoimmune hepatitis, nonalcoholic fatty liver disease,
alcoholic liver disease, etc.); Patients were classified as grade A/mild (Child-Pugh
score: 5-6) or grade B/moderate (Child-Pugh score: 7-9) according to the Child-Pugh
classification within 72 hours before taking the study drug; Among them, the
researchers used standard diagnosis and treatment methods, combined with the patient's
past medical history, laboratory tests, liver biopsy or imaging examination and other
documents to diagnose chronic liver function impairment, and then evaluated according
to the Child-Pugh classification.
5. (Inquiry) patients who have a stable medication plan for the treatment of liver
function impairment, complications, and other concomitant diseases for at least 28
days (or 14 days for patients with moderate liver function) before taking the study
drug, and who do not need to adjust the medication (including the type, dose, or
frequency of medication); Or those who do not use drugs;
6.In addition to liver function damage and complications, the investigators were in
good physical condition according to medical history inquiry, vital signs, physical
examination, laboratory tests (blood routine, urine routine, stool routine, blood
biochemistry, coagulation function, blood pregnancy (only female), 12-lead
electrocardiogram, chest X-ray, abdominal color Doppler ultrasound,
electroencephalogram, etc.), and no other clinically significant abnormalities.
Exclusion Criteria:
- 1. (Inquiry) The subject has any of the following conditions: previous liver
transplantation; Severe portal hypertension or transsurgical portosystemic shunt;
Patients with suspected or confirmed liver cancer or other malignant tumors; Patients
with hepatorenal syndrome; Biliary cirrhosis, biliary obstruction, cholestatic liver
disease and other diseases that seriously affect bile excretion; Patients with
complications such as hepatic encephalopathy (according to Child-Pugh criteria), liver
failure, esophageal and gastric varices bleeding, severe/advanced ascites or pleural
effusion requiring puncture drainage and albumin supplementation, who were considered
by the investigator to be unsuitable;
2. (Inquiry) In addition to the disease causing liver function impairment, patients
with serious acute or chronic diseases of other important organs within 1 year before
screening, including but not limited to neuropsychiatric, gastrointestinal,
respiratory, urinary, endocrine, hematological, immune and other diseases, judged by
the investigator to be not suitable for the trial;
3. (Inquiry) Any of the following occurred within 6 months prior to study entry:
Myocardial infarction, Congenital long QT syndrome, Torsades de pointes (including
sustained ventricular tachycardia and ventricular fibrillation), right bundle branch
block and left anterior hemiblock (bifascicular block), Unstable angina pectoris,
coronary artery/peripheral artery bypass grafting, New York Heart Association (NYHA)
class III or IV congestive heart failure, cerebrovascular accident, transient ischemic
attack, or pulmonary embolism;
4. (asking) a history of depression or suicidal tendencies;
5. (Inquiry) patients who had severe gastrointestinal diseases (except secondary
gastrointestinal diseases caused by hepatitis) or had digestive system surgery within
3 months before screening, and the investigators thought that the absorption of drugs
was affected;
6. (Inquiry) patients who lost blood or donated more than 400mL of blood within one
month before screening, or received red blood cell transfusion;
7. (Inquiry) Liver function fluctuation (e.g., active hepatitis), rapid deterioration
(e.g., advanced ascites, fever, active gastrointestinal bleeding), CTCAE 5.0 common
adverse event grade = 2, ongoing arrhythmia, atrial fibrillation of any grade during
screening;
8.The screening laboratory test results met any of the following: (a) alanine
aminotransferase (ALT) >5 times the normal value; (b) neutrophil count <1.0×109/L; (c)
hemoglobin (HGB) <90 g/L; (d) platelet level <50×109/L; (e) subjects with
alpha-fetoprotein (AFP) >50 ng/mL and suspected hepatocellular carcinoma;
9. (Inquiry) patients with specific allergic history (asthma, urticaria, eczema,
etc.), or allergic condition (such as allergic to two or more drugs, foods or
pollens), or known allergic to PDE4 inhibitors (such as apast, roflumilast, etc.);
10. (inquiry) those who had a history of drug abuse in the past 5 years or drug abuse
in the past 3 years before screening;
11. Screen-positive for drug abuse (except those screen-positive for drug abuse due to
concomitant medication);
12. Positive breath alcohol test (alcohol concentration >0mg/L);
13. (Inquiry) who consumed more than 14 units of alcohol per week in the 3 months
before screening (1 unit = 17.7 mL ethanol, i.e. 1 unit = 354 mL of 5% beer or 44 mL
of 40% liquor or 147 mL of 12% wine), or who could not abstain from alcohol during the
study;
14. (Inquiry) who smoked more than 5 cigarettes per day in the 3 months before
screening, or who could not stop using any tobacco products during the study;
15. (Inquiry) subjects who consumed excessive amounts of tea, coffee and/or
caffeine-rich beverages (more than 8 cups, 1 cup =250 mL) per day in the previous 3
months;
16. Having one or more of the tests for hepatitis B, C, HIV and syphilis clinically
significant;
17. (Inquiry) who participated in clinical trials of other drugs/devices within 3
months before screening and used the trial drugs/devices;
18. (Inquiry) who had received drugs with definite potential hepatotoxicity (such as
acetaminophen, statins, azithromycin, dapsone, clarithromycin, fluconazole,
ketoconazole, rifampicin, etc.) for 7 consecutive days or more within 3 months before
screening;
19. (Inquiry) Use of any drugs (e.g., inductors-barbiturates, pioglitazone,
carbamazepine, phenytoin, glucocorticoids) that induce or inhibit hepatic
drug-metabolizing enzymes within 30 days before screening; Inhibitors: SSRI
antidepressants, cimetidine, diltiazem macrolides, nitroimidazole, sedative hypnotics,
verapamil, fluoroquinolones, antihistamines, isoniazid);
20. (Inquiry) who used prescription drugs, over-the-counter drugs, health supplements,
herbal products or vaccines other than those used for liver function impairment and
other concomitant diseases within 2 weeks before screening;
21. (Inquiry) any caffeine/xanthine/food or drink (such as strong tea, coffee,
chocolate, cola, animal organs, grapefruit, dragon fruit, mango, etc.) rich in
caffeine/xanthine/may affect the absorption, distribution, metabolism, excretion of
drug in the judgment of the investigator during the period from screening to day -1 of
admission, or unable to stop the intake of the above food or drink during the trial;
22. (Asking) pregnant or lactating women, or subjects (including male subjects) who
have plans to give birth or donate sperm or eggs from two weeks before the trial to
six months after the last dose of drug, unwilling or not to take effective
contraceptive measures;
23. (inquiry) those who are unable to eat or have swallowing difficulties, have
special dietary requirements and/or cannot follow a uniform diet;
24. (inquiry) with a history of epileptic seizures;
25. (Inquiry) Those who cannot tolerate venipuncture and/or have a history of dizzy
with blood and needles;
26. Subjects with other factors considered by the investigator to be ineligible for
the trial.
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