A Phase III Study to Evaluate the Efficacy and Safety of Intravenous Infusion of Nemonoxacin in Treating CAP

A Multi-center, Randomized, Double-Blind, Parallel Comparative, Phase III Study to Evaluate the Efficacy and Safety of Intravenous Infusion of Nemonoxacin Versus Levofloxain in Treating Adult Patients With CAP

The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of intravenous nemonoxacin compared with intravenous moxifloxacin in adult patients with community-acquired pneumonia (CAP).

Study Overview

• Status: Completed
• Conditions: Community-acquired Pneumonia
• Intervention / Treatment: Drug: Levofloxacin; Drug: Nemonoxacin

Detailed Description

Community-acquired Pneumonia (CAP) remains a leading cause of death in both developing and developed countries. In the choice of antibacterial agents used to treat CAP, fluoroquinolones have received considerable attention because of their wide spectrum of bactericidal activity. TG-873870 (Nemonoxacin), a non-fluorinated quinolone (NFQ), is a selective bacterial topoisomerase inhibitor.

This study will evaluate the clinical efficacy, microbiological efficacy and safety of Intravenous nemonoxacin compared with Intravenous levofloxacin in adult patients with community-acquired pneumonia.

Besides, the populationpharmacokinetics (PPK) of nemonoxacin in adult patients with CAP after continuous IV Infusion and the pharmacokinetic (PK)/pharmacodynamic (PD)are to be determined.

• Study Type: Interventional
• Enrollment (Actual): 598
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baotou, China
    • Baotou Central Hospital
  • Beijing, China
    • Peking University People's Hospital
  • Beijing, China
    • Chinese People's Liberation Army General Hospital
  • Beijing, China
    • Aerospace Center Hospital
  • Beijing, China
    • Affiliated Beijing Anzhen Hospital of Capital Medical University
  • Beijing, China
    • Affiliated Beijing Chaoyang Hospital of Capital Medical University
  • Beijing, China
    • Institute of Clinical Pharmacology, Peking University
  • Changsha, China
    • The Third Xiangya Hospital of Central South University
  • Changsha, China
    • Changsha Central Hospital
  • Changsha, China
    • The Third Changsha Hotpital
  • Chongqing, China
    • Daping Hospital
  • Guangxi, China
    • Guangxi Zhuang Autonomous Region People's Hospital
  • Guangzhou, China
    • First Affiliated Hospital of Guangzhou Medical University
  • Guilin, China
    • Guilin Medical School Affiliated Hospital
  • Haikou, China
    • Hainan General Hospital
  • Hangzhou, China
    • The Second Affiliated Hospital of Zhejiang University
  • Hangzhou, China
    • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
  • Hefei, China
    • The First Hospital of Anhui Medical University
  • Hohhot, China
    • The Affilated Hospital of Inner Mongolia Medical University
  • Jilin, China
    • The First Hospital of Jilin University
  • Jilin, China
    • The Fourth Hospital of Jilin University
  • Jinan, China
    • Jinan Central Hospital
  • Jinan, China
    • The Second Hospital of Shandong University
  • Lanzhou, China
    • Gansu Provincial People's Hospital
  • Nanchang, China
    • Jiangxi Provincial People's Hospital
  • Nanchang, China
    • Second Subsidiary Hospital of Nanchang Medical College
  • Nanjing, China
    • General Hospital of Nanjing Military Command
  • Shanghai, China
    • Shanghai Pulmonary Hospital
  • Shanghai, China, 200040
    • Institute of Antibiotics, Huashan Hospital, Fundan University
  • Shanghai, China
    • Huadong Hospital affiliated to Fudan University
  • Shanghai, China
    • Shanghai East Hospital of Tongji University
  • Shenyang, China
    • Shengjing Hospital
  • Shenyang, China
    • General Hospital of Shenyang Military
  • Shenzhen, China
    • ShenZhen People's Hospital
  • Shenzhen, China
    • The second people's Hospital of Shenzhen
  • Sichuan, China
    • General Hospital of Chengdu Military Region
  • Sichuan, China
    • West China Center of Medical Sciences of Sichuan University
  • Taiyuan, China
    • First Hospital Of ShanXi Medical University
  • Wuxi, China
    • WuXi People's Hospital
  • Xi'an, China
    • Tangdu Hospital
  • Xiamen, China
    • The First Affilated Hospital of Xiamen University
  • Yangzhou, China
    • Northern Jiangsu People's Hospital
  • Zhejiang, China
    • The First Affiliated Hospital,College of Medicine,Zhejiang University
• Taiwan
  • Chang Hua, Taiwan
    • Changhua Christian Hospital
  • Chiayi City, Taiwan
    • Chiayi Chang Gung Memorial Hospital
  • Hsinchu, Taiwan
    • NTUH Hsin-Chu Branch
  • Hualien City, Taiwan
    • Hualien Tzu Chi Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Veterans General Hospital
  • Keelung, Taiwan
    • Keelung Chang Gung Memorial Hospital
  • New Taipei City, Taiwan
    • Mackay Memorial Hospital
  • New Taipei City, Taiwan
    • Far Eastern Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taichung, Taiwan
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan
    • Chi Mei Hospital, Liouying
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Municipal Wanfang Hospital
  • Taipei, Taiwan
    • Taipei Medical University Hospital
  • Taipei, Taiwan
    • Taipei Medical University - Shuang Ho Hospital
  • Yuli, Taiwan
    • NTUH Yun-Lin Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ages between 18 and 80;
2. Weighs between 40 ~ 100 kg, and BMI ≥ 18 kg/m2;
3. Must have a clinical diagnosis of CAP
4. Chest X-ray and /or CT scan show new or persist/progressive infiltrates
5. Patients with PORT/PSI score II, III or IV.
6. If female, non-lactating and at no risk or pregnancy (post-menopausal or must use adequate birth control)
7. Male must use a reliable form of contraception.
8. Able to receive an intravenous infusion of the drug
9. Able to provide an adequate sputum and blood samples
10. Able to provide written informed consent

Exclusion Criteria:

1. Patients with PORT/PSI score I or VI.
2. Severe CAP is present if a patient needs invasive mechanical ventilation or requires vasopressors.
3. Healthcare-associated pneumonia, hospital-acquired pneumonia, or hospitalized within 14 days before enrollment
4. Virus pneumonia, aspiration pneumonia, ventilator associated pneumonia, or intersstitial lung disease
5. Bronchial bostruction (exclusive of COPD), bronchiectasis, cystic fibrosis, known or suspected pneumocystis pneumonia, known or suspected tuberculosis, primary empyema thoracis, lung abscess, known or suspected lung cancer, or lung disease associated with autoimmune disorders.
6. Medical history of QT prolongation, require the treatment of arrhythmia using class IA or class III drugs, or NYHA functional class >/= III
7. Clinically significant findings on 12-lead ECG, QTc interval>450ms or potassium is < 3.5 mmol/L or lower limit of normal at Screening
8. Immunocompromising illness, such as HIV infection
9. Fatal progressive disease or neurodegenerative diseases that prevent patients from effectively clearing pulmonary secretions
10. Have medical history of seizure, alcohol or drug abuse, suicide tendency, or psychosis that can effect the compliance
11. Have diseases that may affect intravenous infusion.
12. Active hepatitis or decompensated cirrhosis with ascites (Child-Pugh score 10-15/class C);
13. Renal Insufficiency or creatinine >/= 1.1 ULN within 24 hr before first dose
14. ALT or AST >/= 3x ULN, or BUN >/= 30 mg/dL within 24 hr before first dose
15. Neutrophil < 1000 mm3 within 24 hr before first dose
16. Received systemic antibiotics within 72 hr before first dose
17. Received probenecid within 24 hr before first dose or require the treatment with probenecid during study
18. Received quinolones or fluoroquinolones within 14 days before first dose
19. Received any investigational drugs within 30 days before first dose
20. Require the treatment with other systemic antibiotics during study
21. Patients who are being or will be on a long-term medication (over 2 weeks) of steroids (20mg/day)
22. Medical history of hypersensitivity to any quinolone, fluoroquinolone-associated tendinitis and tendon rupture, or myasthenia gravis
23. Current condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the data
24. Participated and received the study medication in previous clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nemonoxacin 500 mg; Nemonoxacin 500mg/250mL, intravenous administration, once daily for 7~14 days	Drug: Nemonoxacin
Active Comparator: Levofloxacin 500mg; Levofloxacin: 500mg/100mL, intravenous administration, once daily for 7~14 days	Drug: Levofloxacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Per subject clinical cure rate	The clinical cure rate will be evaluated according to signs and symptoms and changes in the chest X-ray	end of treatment and 7 to 14 days after the end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Per subject microbiological cure rate	The microbiological cure rate will be evaluated according to the microbiological identification results of the central laboratory	end of treatment and 7 to 14 days after the end of treatment
Per subject overall cure rate	Evaluate the overall efficacy after a comprehensive consideration of the clinical results and the bacteriological results.	end of treatment and 7 to 14 days after the end of treatment
Safety evaluation	Incidence and severity of AE and changes in safety parameters from baseline	duration of trial

Collaborators and Investigators

• Sponsor: TaiGen Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): May 4, 2017
• Study Completion (Actual): May 15, 2017

Study Registration Dates

• First Submitted: July 27, 2014
• First Submitted That Met QC Criteria: July 29, 2014
• First Posted (Estimate): July 31, 2014

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: community-acquired pneumonia; intravenous nemonoxacin
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Ofloxacin
• Other Study ID Numbers: TG-873870-C-6