| Eligibility |
Inclusion Criteria:
-
Participants with mild to moderate liver impairment must meet all of the following criteria
to enter the study:
- The informed consent is signed before the trial, and the content, process and possible
adverse reactions are fully understood; Be able to complete the study according to the
requirements of the test scheme;
- Only for male, subjects aged 18 to 75 years (including both ends) on the date of
signing informed consent;
- The body weight subjects is no less than 50 kg. Body mass index (BMI) is in the range
of 19.0 kg/m2-29.0 kg/m2 (including the critical value);
- Primary liver disease (except for drug-induced liver injury) is necessary for patients
with liver impairment, then patients with mild liver impairment (Child-Pugh score:
5-6) who are assessed as grade A according to Child-Pugh classification must be taken
the clinical stability was = 28 days before taking the experimental drug; while
patients with moderate liver impairment (Child-Pugh score: 7-9) who are assessed as
grade B according to Child-Pugh classification must be taken the clinical stability
was = 14 days before taking the experimental drug;
- Patients who have stable medication regimen for liver impairment, complications and
other concomitant diseases within at least 28 days before taking the experimental
drug, and the medication does not need to be adjusted (including drug type, dosage or
frequency) during the clinical trials; or those who do not use the drug;
- The function of vital organs meets the following criteria: Absolute neutrophil count
(ANC) = 1.0 × 109 / L (1000 / mm3); Hemoglobin (Hgb) = 9.0 g / dL (90g / L); Platelet
= 75.0 × 109 / L (75000 / mm3); Creatinine clearance rate (CLcr) = 80 mL / min; The
corrected QTc interval (QTcF) was less than 450 msec (male);
- In addition to liver impairment and complications, the investigator judged good
condition according to the history inquiry, vital signs, physical examination, routine
laboratory examination, 12-lead ECG, abdominal ultrasound scan, EEG, etc., and there
was no other clinically significant abnormality;
- Male subjects are willing to have no family planning during the trial and within 6
months after the last administration of the trial drug, and voluntarily take effective
contraceptive measures, or have undergone surgical sterilization.
Exclusion Criteria:
-
Participants with mild to moderate liver impairment who meet any of the following criteria
will not be eligible for this study:
- Subjects had any of the following conditions: Patients with hepatic encephalopathy
(according to Child-Pugh score); previous liver transplantation; severe portal
hypertension or portal systemic shunt; suspected or diagnosed liver cancer or other
malignant tumors; liver failure patients; esophageal and gastric variceal bleeding;
severe / advanced ascites; hepatorenal syndrome patients; biliary tract Liver
cirrhosis, biliary obstruction, cholestatic liver disease and other diseases that
seriously affect bile excretion;
- In addition to the diseases leading to the diagnosis of liver impairment, the patients
with severe acute and chronic diseases of other important organs within one year
before screening, including but not limited to neuropsychiatric, digestive tract,
respiratory system, urinary, endocrine, blood, immune and other diseases, were judged
by the researchers to be unsuitable for the trial;
- Any of the following conditions occurred within 6 months prior to the study:
myocardial infarction, congenital long QT syndrome, torsade de pointes (including
persistent ventricular tachycardia and ventricular fibrillation), right bundle branch
block and left anterior half block (bifascilar block), unstable angina pectoris,
coronary / peripheral artery bypass grafting, and congestive heart failure syndrome
(Grade III or IV according to NYHA), cerebrovascular accident, transient ischemic
attack, or pulmonary embolism;
- Patients who had serious gastrointestinal diseases (except secondary gastrointestinal
diseases caused by hepatitis) or had digestive system surgery 3 months before
screening, and the researchers considered that drug absorption was affected;
- Warfarin or related coumarins were used for anticoagulant therapy within one month
before screening, or warfarin or related coumarins were required for anticoagulant
therapy during the trial period;
- During the screening period, liver function fluctuations (such as active hepatitis),
rapid deterioration (such as advanced ascites, fever, active gastrointestinal
bleeding), NCI CTCAE grade 2 or above, ongoing arrhythmia, and atrial fibrillation of
any level occurred;
- People with allergic constitution, including those with severe drug allergy or history
of drug allergy, and patients known to be allergic to the study drug SHR3680 or any
excipients of the product;
- Those who have a history of drug use, or have a history of drug abuse in the past five
years, or have a positive drug screening (except those with drug screening positive
due to concomitant drug use);
- HIVAb positive, syphilisAb positive;
- Patients who have taken any clinical trial drugs within 3 months before screening; 14)
Patients who had received drugs with definite potential hepatotoxicity and used them
continuously for 7 days or more within 3 months before taking experimental drug;
- In 2 weeks before screening, they used traditional Chinese medicine (Chinese herbal
medicine, Chinese patent medicine), dietary supplements and vitamins;
- Subjects with other factors not suitable to participate in this study were considered
by the investigator.
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