Pharmacokinetics Study of Nemonoxacin Malate Capsules in Subjects With Severe Impaired Renal Function

NCT02840812 | Unknown Phase 1

• 1 other identifier: XCNN-150830-2
• Study Type: interventional
• Target: 24
• 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 severe renal function impaired (eGFR≤30mL/min/1.73m2，CKD-EPI estimated) subjects in age, gender and weight as parallel control, which matches healthy with normal renal function according to the of subjects with impaired renal function as, after enrollment of subjects with severe impaired renal function (eGFR≤30mL/min/1.73m2，CKD-EPI estimated). Renal 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

Kidney Dysfunction

Outcome Measures

Primary Outcomes (10)

• Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in severe impaired renal 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 severe impaired renal 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 severe impaired renal 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 severe impaired renal 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 severe impaired renal 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 severe impaired renal 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 severe impaired renal 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 severe impaired renal 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 severe impaired renal Function::renal clearance of the drug from plasma (CLr)

  Within 72h after dosing

• Pharmacokinetics (PK) parameters of single oral dose of nemonoxacin in severe impaired renal 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 (8)

• Safety assessed by AEs

  up to 72 hours after study drug dosing

• Safety assessed by vital signs-respiratory rate

  up to 72 hours after study drug dosing

• Safety assessed by vital signs-body temperature

  up to 72 hours after study drug dosing

• Safety assessed by vital signs-blood pressure

  up to 72 hours after study drug dosing

• Safety assessed by vital signs-pulse rate

  up to 72 hours after study drug dosing

Study Arms (2)

Renal function impaired

EXPERIMENTAL

Subject with Severe Impaired Renal 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

Nemonoxacin Malate Capsules 500mg single dose oral

Also known as: Nemonoxacin Malate Capsules

Healthy Subjects; Renal 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 kidney impairment
• male or female aged 18 to 70 years；
• has a body mass index of 17 to 30 kg/m2;
• Patients with severe impaired renal function or end-stage renal disease (eGRF≤30ml/min/1.73m2, CKD-EPI estimated),and don't have hemodialysis.
• 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 (4) 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 renal impairment
• Male or female volunteers (matched to a subject with renal impairment in gender）；
• Aged 18 to 70 years (matched to a subject with renal impairment±5 years, matched range cannot exceed±5 years)；

You may not qualify if:

• Subjects with kidney impairment
• Has known or suspected allergies to quinolones, fluoroquinolones,Nemonoxacin or excipients or allergic constitution；
• Has diseases (e.g. unstable cardiac disease, uncontrolled hypertension, uncontrolled asthma, uncontrolled diabetes, uncontrolled thyroid disease, uncontrolled epilepsy, myasthenia gravis or other neuromuscular disease, which may affect PK profile of drug in vivo or increase the risk in study except the disease caused renal function impaired;
• Has moderate or severe anemia (Hb\<60g/L), severe hypertension (SBP\>180mmHg and/or DBP\>110mmHg) or diabetic nephropathy;
• 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；
• Scr changes exceed more than 30% compared with baseline (Renal function tests two weeks before screening period ,even not conducted in this study can performed as baseline);
• Has uracratia or anuria;
• Has significant drug change including prescription drugs, non-prescription drugs or nutritional regimen 2 weeks before dosing(judged by investigator);
• Has administration of drug which eliminated mainly via kidney or damage kidney 2 weeks before dosing or need combination use in the study (e.g. TMP-SMZ or non-steroid anti-inflammatory drug);
• Has a history of alcoholism within 2 years prior to dosing; drink≥12 times within 3 months prior dosing; alcohol test positive as screening；
• Has history of drug misuse within 2 years prior to dosing; urine drug screen positive；
• 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;
• Use of another investigational drug or drug which can damage hepatic function within 3 months prior to dosing；
• Has history of blood donation 3 months before study;

Sponsors & Collaborators

• Zhejiang Medicine Co., Ltd.: lead

Study Sites (1)

ZheJiang Medicine

Shaoxing, China

RECRUITING

MeSH Terms

Interventions

nemonoxacin

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: July 19, 2016
• First Posted: July 21, 2016
• Study Start: April 5, 2017
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: April 3, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)