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| Name | Class |
|---|---|
| Huashan Hospital | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Liver function impaired | Experimental | Subject with Moderate Impaired Hepatic Function. Nemonoxacin Malate Capsules 500mg single dose oral. |
|
| Healthy Subjects | Experimental | Healthy volunteers. Nemonoxacin Malate Capsules 500mg single dose oral. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nemonoxacin | Drug | Single dose 500mg oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function: maximum plasma drug concentration ( Cmax) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing | |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function: time at which maximum plasma concentration is observed (Tmax) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing | |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function: area under the plasma concentration vs. time curve (AUC0-t and AUC0-∞) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing | |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function:elimination half-life (t1/2) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing | |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function:mean dissolution time (MRT) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing | |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function: total clearance of the drug from plasma (CLz/F) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing | |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function: Apparent Volume of Distribution (Vz/F) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Safety assessed by AEs | reported spontaneously or not by leading questions | up to 72 hours after study drug dosing |
| Safety assessed by vital signs | blood pressure, pulse rate, respiratory rate and body temperature |
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Inclusion Criteria:
Subjects with hepatic impairment
male or female aged 18 to 70 years;
has a body mass index of 17 to 30 kg/m2;
eGRF>50ml/min/1.73m2;
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;
B-ultrasonography, CT or MRI shows or biopsy confirm that have a positive diagnosis of cirrhosis ;
Has stable regimen of treatment of hepatic function impaired for 3 months prior to enrollment;
Female volunteers must meet:
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;
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;
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;
Can sign informed consent form on his own accord;
Can comply with study procedures
Healthy subjects without hepatic impairment
Male or female volunteers (matched to a subject with hepatic impairment in gender);
Aged 18 to 70 years (matched to a subject with hepatic impairment±5 years, matched range cannot exceed±5 years);
Has a body mass index of 17 to 30 kg/m2(matched to a subject with hepatic impairment±15%,matched range cannot exceed±15%);
Must be in good health as determined by screening medical history, physical examination, vital signs, laboratory test, B ultrasonography and chest X ray;
Female volunteers must meet:
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;
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;
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;
Can sign informed consent form on his own accord;
Can comply with study procedures
Exclusion Criteria:
Subjects with hepatic impairment
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| Name | Affiliation | Role |
|---|---|---|
| Jing Zhang, Doctor | Huashan Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huashan Hospital, Fudan University | Shanghai | Shanghai Municipality | 20040 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30819510 | Derived | Kang Y, Li Y, Xu F, Zhang J, Wang K, Chen Y, Wu J, Guo B, Yu J, Zhang Y. Population Pharmacokinetics Study of Nemonoxacin Among Chinese Patients With Moderate Hepatic Impairment. Clin Ther. 2019 Mar;41(3):505-517.e0. doi: 10.1016/j.clinthera.2019.01.015. Epub 2019 Feb 26. |
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| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C543520 | nemonoxacin |
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| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function: cumulative amount of unchanged drug excreted into the urine (Ae Urine 0-24h,0-72h) | Within 72h after dosing |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function:renal clearance of the drug from plasma (CLr) | Within 72h after dosing |
| Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in Moderate Impaired Hepatic Function: minimum plasma drug concentration (Cmin) | Pre-dose, 0.5h,1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h after dosing |
| up to 72 hours after study drug dosing |
| Safety assessed by laboratory tests | Hematology, blood biochemistry,cogulation test and urinalysis | up to 72 hours after study drug dosing |
| Safety assessed by physical examination | (1) general appearance (2) skin (3) head and neck (4)chest, including heart, pulmonary and breast (5) abdomen, including stomach and intestines, liver and gallbladder (6) back (7) Urinary tract (8) extremity (9) neurological or psychiatric system (10) lymph gland (11)others. | up to 72 hours after study drug dosing |
| Safety assessed by 12-lead ECGs | up to 72 hours after study drug dosing |