Pharmacokinetics Study of Nemonoxacin Malate Capsules in Subjects With Moderate Impaired Hepatic Function

NCT02604498 | Completed Phase 1

• 1 other identifier: XCNN-150830-1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Liver Dysfunction

Outcome Measures

Primary Outcomes (10)

• 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

• 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

Secondary Outcomes (5)

• Safety assessed by AEs

  up to 72 hours after study drug dosing

• Safety assessed by vital signs

  up to 72 hours after study drug dosing

• Safety assessed by laboratory tests

  up to 72 hours after study drug dosing

• Safety assessed by physical examination

  up to 72 hours after study drug dosing

• Safety assessed by 12-lead ECGs

  up to 72 hours after study drug dosing

Study Arms (2)

Liver function impaired

EXPERIMENTAL

Subject with Moderate Impaired Hepatic Function. Nemonoxacin Malate Capsules 500mg single dose oral.

Drug: Nemonoxacin

Healthy Subjects

EXPERIMENTAL

Healthy volunteers. Nemonoxacin Malate Capsules 500mg single dose oral.

Drug: Nemonoxacin

Interventions

Nemonoxacin DRUG

Single dose 500mg oral

Also known as: Nemonoxacin Malate Capsules

Healthy Subjects; Liver function impaired

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Has sterilization operation, or who are postmenopausal must have been postmenopausal for \>1 year, or
• 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;
• 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

You may not qualify if:

• Subjects with hepatic impairment
• Has known or suspected allergies to quinolones, fluoroquinolones, Nemonoxacin or excipients or allergic constitution；
• Has acute disease or chronic disease which may affect PK profile of drug in vivo except the disease caused hepatic function impaired；
• Has abnormal result of laboratory tests with clinical significance except which caused by the disease of hepatic function impaired；
• Has history of clinically significant cardiovascular, neurological or psychiatric, gastrointestinal, pulmonary, renal, endocrine disease prior to study within 1 year；
• Has disease seriously affect the immune system such as hematological disease, malignant tumor, or taking immunosuppressant；
• Has acute or sub-acute hepatic function failure；
• Has experienced esophageal variceal bleeding within the past 6 months；
• Has advanced ascites or spontaneous bacterial peritonitis；
• Has a history of Gilbert's disease；
• Has resistance or liver function abnormal after orally taking nucleoside analogue, an antiviral drug；
• Stop taking nucleoside analogue, an antiviral drug within 1 year；
• Has total bilirubin\>3×upper limit of normal (ULN) and without cholestasis; alkaline phosphatase (ALP)\>2×ULN；
• Alanine Aminotransferase (ALT)or Aspartate Aminotransferase（AST）\>5×ULN；
• ALT or AST\>3×ULN with total bilirubin\>2×ULN；

Sponsors & Collaborators

• Zhejiang Medicine Co., Ltd.: lead
• Huashan Hospital: collaborator

Study Sites (1)

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, 20040, China

Location

Related Publications (1)

• 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.

  PMID: 30819510 DERIVED

MeSH Terms

Conditions

Liver Diseases

Interventions

nemonoxacin

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Jing Zhang, Doctor

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 13, 2015
• Study Start: April 14, 2016
• Primary Completion: January 15, 2018
• Study Completion: January 15, 2018
• Last Updated: March 30, 2018

Record last verified: 2018-03

Locations

CN (1)