Pharmacokinetics Study of Nemonoxacin Malate Capsules in Subjects With Moderate Impaired Hepatic Function
Pharmacokinetics Study of Nemonoxacin Malate Capsules in Subjects With Moderate Impaired Hepatic Function
This is a single center, open-label, non-randomized, 1:1 parallel control and single dose
 administration study design. Healthy subjects will be matched to moderate hepatic function
 impaired (Child-Pugh B，7-9) subjects in age, gender and weight as parallel control, which
 matches healthy with normal hepatic function according to the of subjects with impaired
 hepatic function as, after enrollment of subjects with moderate impaired hepatic function
 (Child-Pugh B，7-9). Hepatic function impaired group and control group both receive orally
 single-dose of nemonoxacin malate capsule (0.5g). Collect the blood and urine samples before
 and after the administration to perform pharmacokinetic analysis and safety observation.
Single dose study: evaluate safety and tolerability of oral nemonoxacin capsule 500mg.
Inclusion Criteria:

 -  Subjects with hepatic impairment

 1. male or female aged 18 to 70 years；

 2. has a body mass index of 17 to 30 kg/m2；

 3. eGRF>50ml/min/1.73m2；

 4. Patients in stable condition with moderate impaired hepatic function, due to
 viral hepatitis, alcoholic liver disease, autoimmune hepatitis, primary biliary
 cirrhosis or other causes, and determined to be level B according to Child-Pugh
 classification；

 5. B-ultrasonography, CT or MRI shows or biopsy confirm that have a positive
 diagnosis of cirrhosis ；

 6. Has stable regimen of treatment of hepatic function impaired for 3 months prior
 to enrollment;

 7. Female volunteers must meet:

 1. Has sterilization operation, or who are postmenopausal must have been
 postmenopausal for >1 year, or

 2. Has childbearing potential, but meet the requirement as following:

 Negative pregnancy test prior to enrollment, and Agree with use 1 medical
 accepted methods of birth control (eg. Hormonal contraceptive, barrier
 contraceptive with additional spermicide, or an intrauterine device) during the
 whole study and continuing until 1 month after the end of the study, and
 Non-breastfeeding;

 8. Male volunteers must agree to use medical accepted method of birth control (e.g.
 barrier contraceptive or sexual partner use the method as (7) above) during the
 study and through 1month after the end of study；

 9. Agree stay in ward prior to dosing within 48h, and agree not to take coffee, tea,
 chocolate, alcohol, grapefruit juice, orange juice and other food and drink which
 contain caffeine and xanthine；

 10. Can sign informed consent form on his own accord；

 11. Can comply with study procedures

 Healthy subjects without hepatic impairment

 1. Male or female volunteers (matched to a subject with hepatic impairment in gender）；

 2. Aged 18 to 70 years (matched to a subject with hepatic impairment±5 years, matched
 range cannot exceed±5 years)；

 3. Has a body mass index of 17 to 30 kg/m2（matched to a subject with hepatic
 impairment±15%，matched range cannot exceed±15%）；

 4. Must be in good health as determined by screening medical history, physical
 examination, vital signs, laboratory test, B ultrasonography and chest X ray；

 5. Female volunteers must meet:

 1. Has sterilization operation, or who are postmenopausal must have been
 postmenopausal for >1 year, or

 2. Has childbearing potential, but meet the requirement as following:

 Negative pregnancy test prior to enrollment, and Agree with use 1 medical accepted
 methods of birth control (eg. Hormonal contraceptive, barrier contraceptive with
 additional spermicide, or an intrauterine device) during the whole study and
 continuing until 1month after the end of the study, and Non-breastfeeding；

 6. Male volunteers must agree to use medical accepted method of birth control (e.g.
 barrier contraceptive or sexual partner use the method as (7) above) during the study
 and through 1month after the end of study；

 7. Agree stay in ward prior to dosing within 48h, and agree not to take coffee, tea,
 chocolate, alcohol, grapefruit juice, orange juice and other food and drink which
 contain caffeine and xanthine；

 8. Can sign informed consent form on his own accord；

 9. Can comply with study procedures

 Exclusion Criteria:

 -  Subjects with hepatic impairment

 1. Has known or suspected allergies to quinolones, fluoroquinolones, Nemonoxacin or
 excipients or allergic constitution；

 2. Has acute disease or chronic disease which may affect PK profile of drug in vivo
 except the disease caused hepatic function impaired；

 3. Has abnormal result of laboratory tests with clinical significance except which
 caused by the disease of hepatic function impaired；

 4. Has history of clinically significant cardiovascular, neurological or
 psychiatric, gastrointestinal, pulmonary, renal, endocrine disease prior to study
 within 1 year；

 5. Has disease seriously affect the immune system such as hematological disease,
 malignant tumor, or taking immunosuppressant；

 6. Has acute or sub-acute hepatic function failure；

 7. Has experienced esophageal variceal bleeding within the past 6 months；

 8. Has advanced ascites or spontaneous bacterial peritonitis；

 9. Has a history of Gilbert's disease；

 10. Has resistance or liver function abnormal after orally taking nucleoside
 analogue, an antiviral drug；

 11. Stop taking nucleoside analogue, an antiviral drug within 1 year；

 12. Has total bilirubin>3×upper limit of normal (ULN) and without cholestasis;
 alkaline phosphatase (ALP)>2×ULN；

 13. Alanine Aminotransferase (ALT)or Aspartate Aminotransferase（AST）>5×ULN；

 14. ALT or AST>3×ULN with total bilirubin>2×ULN；

 15. international senstibity index，INR≥1.5 or prothrombin time activity≤40%；

 16. Child-Pugh assessed as C level；

 17. Has a history of alcoholism within 2 years prior to dosing; drink≥12 times within
 3 months prior dosing; alcohol test positive as screening；

 18. Has history of drug misuse within 2 years prior to dosing; urine drug screen
 positive；

 19. Has history of taking products of tobacco or nicotine more than 5 cigarettes/day
 within 1 month prior to dosing, or cannot stop smoking during the study;

 20. Use of another investigational drug or drug which can damage hepatic function
 within 3 months prior to dosing；

 21. Use of drugs affect function of liver metabolism enzyme (e.g. benzene, isopropyl
 amine, the barbiturates benzodiazepines, marijuana, cocaine, opiates and
 phencyclidine) within 30 days prior to dosing ；

 22. Has to take the drug which may affect the PK profile of investigate drug (e.g.
 antacids, sucralfate, metal cation, calcium supplements, warfarin, non-steroidal
 anti-inflammatory drugs, theophylline, cyclosporine, probenecid and cimetidine) ；

 23. Has gastrointestinal disease or malabsorption syndrome affecting drug Absorb；

 24. Has history of seizures or central nervous system disease which the investigator
 considers to interfere with compliancy of protocol; or has risk of suicide；

 25. Clinical significant abnormal 12-lead electrocardiograms (ECGs) at screening (eg.
 atrioventricular block, torsades de pointes ventricular tachycardia (TdT), and
 other types of ventricular tachycardia, ventricular fibrillation, ventricular
 flutter, T wave change with clinical significance or any abnormal results of
 12-lead ECG which affect QTc interphase) ；

 26. HIV or syphilis RPR test positive；

 27. Conditions investigator consider not suitable to be enrolled in the study.
 Healthy subjects without hepatic impairment

 1. Has known or suspected allergies to quinolones, fluoroquinolones, nemonoxacin or
 excipients or allergic constitution；

 2. Has a history of alcoholism within 2 years prior to dosing; drink≥12 times within
 3 months prior dosing; alcohol test positive as screening；

 3. Has history of drug misuse within 2 years prior to dosing; urine drug screen
 positive；

 4. Has history of taking products of tobacco or nicotine more than 5 cigarettes/day
 within 1 month prior to dosing, or cannot stop smoking during the study；

 5. Donated blood or use of another investigational drug within 3 months prior to
 dosing；

 6. Has history of chronic liver, renal, cardiovascular, neurological or psychiatric,
 gastrointestinal, pulmonary, urinary, endocrine disease cannot controlled by
 drugs；

 7. Use of drugs affect function of liver metabolism enzyme within 30 days prior to
 dosing; or need to take medications which may affect the PK profile of
 investigational drug (including: products containing Calcium, aluminum,
 magnesium, iron and zinc, sucralfate, antacid, nutrition supplements, Vitamins
 and metal supplements) during the study；

 8. Is taking any antibacterial agents or prophylaxis or treatment drugs；

 9. HIV-Ab, HBsAg ,HCV-Ab or syphilis RPR positive；

 10. Clinical significant abnormal 12-lead electrocardiograms (ECGs) at screening (eg.
 atrioventricular block, torsades de pointes ventricular tachycardia (TdT), and
 other types of ventricular tachycardia, ventricular fibrillation, ventricular
 flutter, T wave change with clinical significance or QTc>450ms) ；

 11. Has abnormal result of laboratory test with clinical significance assessed by
 investigator at screening；

 12. Has gastrointestinal disease or malabsorption syndrome affecting drug Absorb；

 13. Has history of seizures or central nervous system disease which the investigator
 considers to interfere with compliancy of protocol; or has risk of suicide；

 14. Has any antibacterials, glucocorticoids, immunosuppressive agents or drug may
 damage organs within 14 days prior to dosing；

 15. Cannot orally take drug；

 16. Has history of or currently has disease and condition may affect the safety and
 efficancy assessment of investigational drug judged by investigator；

 17. Is a member of the clinical site personnel directly affiliated with this study；

 18. Conditions investigator consider not suitable to be enrolled in the study.