Study to Evaluate the Efficacy and Safety of Intravenous Infusion With Nemonoxacin Malate Sodium Chloride

Study Overview
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Brief Summary
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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
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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 Moxifloxacin in adult patients with community-acquired pneumonia. Besides, the pharmacokinetics (PK) of Nemonoxacin in adult patients with CAP after continuous IV Infusion and the pharmacokinetic (PK)/pharmacodynamic (PD)are to be determined.

Official Title
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A Multi-Center, Randomized, Double-Blind, Parallel Comparative, Phase II Study to Evaluate the Efficacy and Safety of Intravenous Infusion With Nemonoxacin Versus Moxifloxacin in Treating Adult Patients With Community-Acquired Pneumonia (CAP)

Conditions
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Pneumonia

Intervention / Treatment
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* Drug: Nemonoxacin 500 mg
* Drug: Nemonoxacin 650 mg
* Drug: Moxifloxacin 400 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages between 18 and 75; 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) The patient is able to receive an intravenous infusion of the drug . Exclusion Criteria: Patients with PORT/PSI score I or VI. Severe CAP is present if a patient needs invasive mechanical ventilation or requires vasopressors. Known or suspected severe bronchiectasis, cystic fibrosis, active pulmonary tuberculosis or infection with other mycobacteria or fungi, known bronchial obstruction, a history of post-obstructive pneumonia, other confounding respiratory diseases, such as lung cancer, malignancy metastatic to the lungs, lung abscess, empyema, suspected aspiration pneumonia due to vomiting, or non-bacterial respiratory infection (chronic obstructive pulmonary disease [COPD] is not exclusionary) Clinically significant conduction or other abnormality on 12-lead ECG, or QTc interval Potassium is < 3.5 mmol/L Any known disease that seriously affect the immune system Active hepatitis or decompensated cirrhosis; Have used quinolones or fluoroquinolones within 14 days before enrollment Patients who are being or will be on a long-term medication of steroids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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. | Drug: Nemonoxacin 500 mg<br>* IV Infusion, once daily for 7 14 days<br>|
| Experimental: Nemonoxacin 650 mg<br>Nemonoxacin 650 mg/325mL | Drug: Nemonoxacin 650 mg<br>* IV Infusion, once daily for 7 14 days<br>|
| Active Comparator: Moxifloxacin 400 mg<br>Moxifloxacin 400mg/250mL | Drug: Moxifloxacin 400 mg<br>* IV Infusion, once daily for 7 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the Clinical Cure Rate of Two Doses of Intravenously Infused Nemonoxacin Malate Sodium Chloride Injection at Visit 4 in the mITT Population | The primary efficacy endpoint of this study was to evaluate whether the clinical cure rate of Nemonoxacin malate sodium chloride is non-inferior to that of Moxifloxacin at visit 4 in the mITT population. At visit 4, the Investigator would assess changes in the symptoms/signs/laboratory tests and chest X-rays/or CT scans associated with this infection, and determined the clinical efficacy in the subjects. The clinical efficacy of the study group and the control group was calculated according to the proportion and percentage of overall clinically cured and clinically ineffective patients in the treatment groups. If the lower limit of the 90% confidence interval for the difference in the clinical cure rate between the study drug and the control drug was larger than -15%, it would be established that the efficacy of Nemonoxacin malate sodium chloride injection was not inferior to that of Moxifloxacin Hydrochloride Sodium Chloride Injection in the treatment of moderate to severe adult CAP. | Visit 1 (baseline, day -1 1) to Visit 4 (7-14 days after stopping the drug) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Number for Microbiologically Cured and Failure at Visit 3 in b-mITT (Bacteriological mITT) Population | Microbiological efficacy at visits 3 would be determined by assessing the identification results from the central laboratory. Subjects must satisfy at least one of the following in order to be evaluated for the microbiological efficacy: Subjects whose respiratory culture from visit 1 was positive; Subjects whose blood culture from visit 1 was positive. The microbiological efficacy at Visit 3 and treatment group (determined by each subject) was determined by the number and percentage of microbiological success subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 3 (Within 24 hours after stopping the drug) | 
| Subject Number for Microbiologically Cured and Failure at Visit 3 in BE (Bacteriological Evaluable) Population | Microbiological efficacy at visits 3 would be determined by assessing the identification results from the central laboratory. Subjects must satisfy at least one of the following in order to be evaluated for the microbiological efficacy: Subjects whose respiratory culture from visit 1 was positive; Subjects whose blood culture from visit 1 was positive. The microbiological efficacy at Visit 3 and treatment group (determined by each subject) was determined by the number and percentage of microbiological success subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 3 (Within 24 hours after stopping the drug) | 
| Subject Number of Success and Failure in Overall Efficacy at Visit 4 in b-mITT (Bacteriological mITT) Population | Only subjects whose bacterial culture from visit 1 was positive would be evaluated for the overall efficacy. The overall efficacy (cured or ineffective) at Visit 4 and treatment group (determined by each subject) was determined by the number and percentage of subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 4 (7-14 days after stopping the drug) | 
| Subject Number of Success and Failure in Overall Efficacy at Visit 4 in BE (Bacteriological Evaluable) Population | Only subjects whose bacterial culture from visit 1 was positive would be evaluated for the overall efficacy. The overall efficacy (cured or ineffective) at Visit 4 and treatment group (determined by each subject) was determined by the number and percentage of subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 4 (7-14 days after stopping the drug) | 
| Subject Number of Success and Failure in Overall Efficacy at Visit 3 in b-mITT (Bacteriological mITT) Population | Only subjects whose bacterial culture from visit 1 was positive would be evaluated for the overall efficacy. The overall efficacy (cured or ineffective) at Visit 3 and treatment group (determined by each subject) was determined by the number and percentage of subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 3 (Within 24 hours after stopping the drug) | 
| Subject Number of Success and Failure in Overall Efficacy at Visit 3 in BE (Bacteriological Evaluable) Population | Only subjects whose bacterial culture from visit 1 was positive would be evaluated for the overall efficacy. The overall efficacy (cured or ineffective) at Visit 3 and treatment group (determined by each subject) was determined by the number and percentage of subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 3 (Within 24 hours after stopping the drug) | 
| Subject Number for Microbiologically Cured and Failure at Visit 4 in b-mITT (Bacteriological mITT) Population | Microbiological efficacy at visits 4 would be determined by assessing the identification results from the central laboratory. Subjects must satisfy at least one of the following in order to be evaluated for the microbiological efficacy: Subjects whose respiratory culture from visit 1 was positive; Subjects whose blood culture from visit 1 was positive. The microbiological efficacy at Visit 4 and treatment group (determined by each subject) was determined by the number and percentage of microbiological success subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 4 (7-14 days after stopping the drug) | 
| Subject Number for Microbiologically Cured and Failure at Visit 4 in BE (Bacteriological Evaluable) Population | Microbiological efficacy at visits 4 would be determined by assessing the identification results from the central laboratory. Subjects must satisfy at least one of the following in order to be evaluated for the microbiological efficacy: Subjects whose respiratory culture from visit 1 was positive; Subjects whose blood culture from visit 1 was positive. The microbiological efficacy at Visit 4 and treatment group (determined by each subject) was determined by the number and percentage of microbiological success subjects. The difference in bacteriological success between Nemonoxacin malate sodium chloride injection and Moxifloxacin Hydrochloride Sodium Chloride Injection was tested using the logistic regression model. | Visit 1 (baseline, day -1 1) to Visit 4 (7-14 days after stopping the drug) | 
| Difference in the Clinical Cure Rate of Two Doses of Intravenously Infused Nemonoxacin Malate Sodium Chloride Injection at Visit 4 in the Clinically Evaluable (CE) Population | The primary efficacy endpoint of this study was to evaluate whether the clinical cure rate of Nemonoxacin malate sodium chloride is non-inferior to that of Moxifloxacin at visit 4 in the CE population. At visit 4, the Investigator would assess changes in the symptoms/signs/laboratory tests and chest X-rays/or CT scans associated with this infection, and determined the clinical efficacy in the subjects. The clinical efficacy of the study group and the control group was calculated according to the proportion and percentage of overall clinically cured and clinically ineffective patients in the treatment groups. If the lower limit of the 90% confidence interval for the difference in the clinical cure rate between the study drug and the control drug was larger than -15%, it would be established that the efficacy of Nemonoxacin malate sodium chloride injection was not inferior to that of Moxifloxacin Hydrochloride Sodium Chloride Injection in the treatment of moderate to severe adult CAP. | Visit 1 (baseline, day -1 1) to Visit 4 (7-14 days after stopping the drug) | 
| Difference in the Clinical Cure Rate of Two Doses of Intravenously Infused Nemonoxacin Malate Sodium Chloride Injection at Visit 3 in the mITT Population | The primary efficacy endpoint of this study was to evaluate whether the clinical cure rate of Nemonoxacin malate sodium chloride is non-inferior to that of Moxifloxacin at visit 3 in the mITT population. At visit 3, the Investigator would assess changes in the symptoms/signs/laboratory tests and chest X-rays/or CT scans associated with this infection, and determined the clinical efficacy in the subjects. The clinical efficacy of the study group and the control group was calculated according to the proportion and percentage of overall clinically cured and clinically ineffective patients in the treatment groups. If the lower limit of the 90% confidence interval for the difference in the clinical cure rate between the study drug and the control drug was larger than -15%, it would be established that the efficacy of Nemonoxacin malate sodium chloride injection was not inferior to that of Moxifloxacin Hydrochloride Sodium Chloride Injection in the treatment of moderate to severe adult CAP. | Visit 1 (baseline, day -1 1) to Visit 3 (Within 24 hours after stopping the drug) | 
| Difference in the Clinical Cure Rate of Two Doses of Intravenously Infused Nemonoxacin Malate Sodium Chloride Injection at Visit 3 in the CE Population | The primary efficacy endpoint of this study was to evaluate whether the clinical cure rate of Nemonoxacin malate sodium chloride is non-inferior to that of Moxifloxacin at visit 3 in the CE population. At visit 3, the Investigator would assess changes in the symptoms/signs/laboratory tests and chest X-rays/or CT scans associated with this infection, and determined the clinical efficacy in the subjects. The clinical efficacy of the study group and the control group was calculated according to the proportion and percentage of overall clinically cured and clinically ineffective patients in the treatment groups. If the lower limit of the 90% confidence interval for the difference in the clinical cure rate between the study drug and the control drug was larger than -15%, it would be established that the efficacy of Nemonoxacin malate sodium chloride injection was not inferior to that of Moxifloxacin Hydrochloride Sodium Chloride Injection in the treatment of moderate to severe adult CAP. | Visit 1 (baseline, day -1 1) to Visit 3 (Within 24 hours after stopping the drug) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moxifloxacin