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

Phase 2

Completed

• Conditions: Pneumonia
• Interventions: Drug: Nemonoxacin 500 mg; Drug: Moxifloxacin 400 mg; Drug: Nemonoxacin 650 mg

• Registration Number: NCT01944774
• Lead Sponsor: TaiGen Biotechnology Co., Ltd.

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 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.

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-08-26
• Study First Submitted QC: 2013-09-13
• Study First Posted: 2013-09-18
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Results First Submitted: 2015-01-08
• Status Verified: 2015-02
• Results First Submitted QC: 2015-02-01
• Last Update Submitted: 2015-02-01
• Results First Posted: 2015-02-18
• Last Update Posted: 2015-02-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 207

Inclusion Criteria

1. Ages between 18 and 75;
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. The patient is able to receive an intravenous infusion of the drug .

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. 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)
4. Clinically significant conduction or other abnormality on 12-lead ECG, or QTc interval
5. Potassium is < 3.5 mmol/L
6. Any known disease that seriously affect the immune system
7. Active hepatitis or decompensated cirrhosis;
8. Have used quinolones or fluoroquinolones within 14 days before enrollment
9. Patients who are being or will be on a long-term medication of steroids

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nemonoxacin 500 mg	Nemonoxacin 500 mg	Nemonoxacin 500mg/250mL.
Moxifloxacin 400 mg	Moxifloxacin 400 mg	Moxifloxacin 400mg/250mL
Nemonoxacin 650 mg	Nemonoxacin 650 mg	Nemonoxacin 650 mg/325mL

Primary Outcome Measures

Name	Time	Method
Difference in the Clinical Cure Rate of Two Doses of Intravenously Infused Nemonoxacin Malate Sodium Chloride Injection at Visit 4 in the mITT Population	Visit 1 (baseline, day -1~1) to Visit 4 (7-14 days after stopping the drug)	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.

Secondary Outcome Measures

Name	Time	Method
Difference in the Clinical Cure Rate of Two Doses of Intravenously Infused Nemonoxacin Malate Sodium Chloride Injection at Visit 3 in the CE Population	Visit 1 (baseline, day -1~1) to Visit 3 (Within 24 hours after stopping the drug)	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.
Subject Number for Microbiologically Cured and Failure at Visit 4 in b-mITT (Bacteriological mITT) Population	Visit 1 (baseline, day -1~1) to Visit 4 (7-14 days after stopping the drug)	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: 1. Subjects whose respiratory culture from visit 1 was positive; 2. 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.
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	Visit 1 (baseline, day -1~1) to Visit 4 (7-14 days after stopping the drug)	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.
Difference in the Clinical Cure Rate of Two Doses of Intravenously Infused Nemonoxacin Malate Sodium Chloride Injection at Visit 3 in the mITT Population	Visit 1 (baseline, day -1~1) to Visit 3 (Within 24 hours after stopping the drug)	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.
Subject Number of Success and Failure in Overall Efficacy at Visit 4 in b-mITT (Bacteriological mITT) Population	Visit 1 (baseline, day -1~1) to Visit 4 (7-14 days after stopping the drug)	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.
Subject Number of Success and Failure in Overall Efficacy at Visit 4 in BE (Bacteriological Evaluable) Population	Visit 1 (baseline, day -1~1) to Visit 4 (7-14 days after stopping the drug)	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.
Subject Number of Success and Failure in Overall Efficacy at Visit 3 in BE (Bacteriological Evaluable) Population	Visit 1 (baseline, day -1~1) to Visit 3 (Within 24 hours after stopping the drug)	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.
Subject Number for Microbiologically Cured and Failure at Visit 3 in b-mITT (Bacteriological mITT) Population	Visit 1 (baseline, day -1~1) to Visit 3 (Within 24 hours after stopping the drug)	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: 1. Subjects whose respiratory culture from visit 1 was positive; 2. 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.
Subject Number for Microbiologically Cured and Failure at Visit 3 in BE (Bacteriological Evaluable) Population	Visit 1 (baseline, day -1~1) to Visit 3 (Within 24 hours after stopping the drug)	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: 1. Subjects whose respiratory culture from visit 1 was positive; 2. 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.
Subject Number of Success and Failure in Overall Efficacy at Visit 3 in b-mITT (Bacteriological mITT) Population	Visit 1 (baseline, day -1~1) to Visit 3 (Within 24 hours after stopping the drug)	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.
Subject Number for Microbiologically Cured and Failure at Visit 4 in BE (Bacteriological Evaluable) Population	Visit 1 (baseline, day -1~1) to Visit 4 (7-14 days after stopping the drug)	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: 1. Subjects whose respiratory culture from visit 1 was positive; 2. 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.

Trial Locations

Locations (2)

Institute of Antibiotics, Huashan Hospital, Fundan University; 🇨🇳 Shanghai, China

Far eastern memorial hospital; 🇨🇳 Taipei, Taiwan