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

Study Overview
=================
Brief Summary
-----------------
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).

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.

Official Title
-----------------
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

Conditions
-----------------
Community-acquired Pneumonia

Intervention / Treatment
-----------------
* Drug: Nemonoxacin
* Drug: Levofloxacin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages between 18 and 80; Weighs between 40   100 kg, and BMI ≥ 18 kg/m2; Must have a clinical diagnosis of CAP Chest X-ray and /or CT scan show new or persist/progressive infiltrates Patients with PORT/PSI score II, III or IV. If female, non-lactating and at no risk or pregnancy (post-menopausal or must use adequate birth control) Male must use a reliable form of contraception. Able to receive an intravenous infusion of the drug Able to provide an adequate sputum and blood samples Able to provide written informed consent Exclusion Criteria: Patients with PORT/PSI score I or VI. Severe CAP is present if a patient needs invasive mechanical ventilation or requires vasopressors. Healthcare-associated pneumonia, hospital-acquired pneumonia, or hospitalized within 14 days before enrollment Virus pneumonia, aspiration pneumonia, ventilator associated pneumonia, or intersstitial lung disease 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. Medical history of QT prolongation, require the treatment of arrhythmia using class IA or class III drugs, or NYHA functional class >/= III Clinically significant findings on 12-lead ECG, QTc interval>450ms or potassium is < 3.5 mmol/L or lower limit of normal at Screening Immunocompromising illness, such as HIV infection Fatal progressive disease or neurodegenerative diseases that prevent patients from effectively clearing pulmonary secretions Have medical history of seizure, alcohol or drug abuse, suicide tendency, or psychosis that can effect the compliance Have diseases that may affect intravenous infusion. Active hepatitis or decompensated cirrhosis with ascites (Child-Pugh score 10-15/class C); Renal Insufficiency or creatinine >/= 1.1 ULN within 24 hr before first dose ALT or AST >/= 3x ULN, or BUN >/= 30 mg/dL within 24 hr before first dose Neutrophil < 1000 mm3 within 24 hr before first dose Received systemic antibiotics within 72 hr before first dose Received probenecid within 24 hr before first dose or require the treatment with probenecid during study Received quinolones or fluoroquinolones within 14 days before first dose Received any investigational drugs within 30 days before first dose Require the treatment with other systemic antibiotics during study Patients who are being or will be on a long-term medication (over 2 weeks) of steroids (20mg/day) Medical history of hypersensitivity to any quinolone, fluoroquinolone-associated tendinitis and tendon rupture, or myasthenia gravis Current condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the data Participated and received the study medication in previous clinical trials

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nemonoxacin 500 mg<br>Nemonoxacin 500mg/250mL, intravenous administration, once daily for 7 14 days | Drug: Nemonoxacin<br> <br> |
| Active Comparator: Levofloxacin 500mg<br>Levofloxacin: 500mg/100mL, intravenous administration, once daily for 7 14 days | Drug: Levofloxacin<br> <br> |

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
intravenous nemonoxacin, community-acquired pneumonia