Efficacy and Safety of Nemonoxacin vs Levofloxacin in Adult Patients With Community-Acquired Pneumonia

Study Overview
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Brief Summary
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The primary objective of this study was to evaluate the clinical efficacy of treatment with Nemonoxacin compared with Tavanic® in patients with community-acquired pneumonia (CAP).

Detailed Description
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Treatment-naive patients with CAP and patients with treatment failure were screened and if met the eligible criteria were randomized to receive either treatment with investigational product or comparator. Patients started to receive intravenous therapy with Nemonoxacin or Tavanic® and then upon a decision of investigator patients were switched to oral therapy with the same product. Intravenous therapy included two consequence infusions (antibiotic solution and placebo solution) to maintain blinding. Intravenous therapy should have been given for at least 3 days and could have been prolonged by a decision of investigator up to 7 days. Then investigator switched a patient from intravenous to oral therapy on Day 4(8) of the study if the specific criteria of clinical stability were achieved. To maintain blinding during oral antibiotic therapy each Tavanic® tablet was placed into a capsule shell (over-encapsulated), that was identical in appearance to a Nemonoxacin-containing capsules. The average duration of treatment (including intravenous and oral therapy) for each patient was 7(14) days and during this period patients should have stayed at hospital. After completion of the treatment patients could have been discharged from the hospital and returned for examinations within 1-2 days after the last dose (end of treatment visit). Then the patients attended the investigational site within 7-9 days after the last dose (test of cure visit). Then the investigator contacted the patients by phone within 21-23 days after the last dose (long-term follow-up visit).

Official Title
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An International, Multicenter, Randomized, Double-blind, Double-dummy, Two-way, Parallel Group, Controlled Study to Compare the Efficacy and Safety of Intravenous and Oral Nemonoxacin Versus Tavanic® in Adult Patients With Community-acquired Pneumonia

Conditions
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Pneumonia, Bacterial

Intervention / Treatment
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* Drug: Nemonoxacin
* Drug: Nemonoxacin
* Drug: Tavanic
* Drug: Tavanic
* Drug: Placebo (250 ml)
* Drug: Placebo (100 ml)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from the patient. Patients with moderate to severe community-acquired pneumonia who need inpatient treatment but do not need intensive care unit treatment. The presence of at least 3 of the following symptoms / signs: cough; purulent sputum production; tachypnea (respiratory rate > 24 breathes/minute); chills; fever (rectal / tympanic temperature ≥ 38.5°C or axillary / oral / skin temperature ≥ 38.5°C); white blood cells (WBC) count of ≥ 10.0 x 10^9/L or ≥ 15% immature neutrophils (bands; regardless of peripheral WBC count). Radiological evidence of (a) new infiltrate(s) consistent with bacterial pneumonia at baseline. Treatment-naive patients or patients who have received single dose of a short-acting antibacterial drug within 24 hours of enrollment or patients with treatment failure who have received antibiotics (with the exception of quinolones or fluoroquinolones) for less than 72 hours. Consent to use contraception during participation in the study (for women of childbearing potential and men). Exclusion Criteria: Known hypersensitivity to quinolones, fluoroquinolones or any of the excipients. Female patients who are pregnant or nursing. History of tendon disease / disorder related to quinolone treatment. Known congenital or documented-acquired QT / QTc(F) prolongation on ECG (QTc(F) interval more than 450 ms); concomitant use of drugs, reported to increase the QT interval; uncorrected hypokalaemia and uncorrected hypomagnesemia; clinically relevant bradycardia; clinically relevant heart failure with reduced left-ventricular ejection fraction; previous history of symptomatic arrhythmias. History of bronchiectasis, cystic fibrosis, bronchial obstructions excluding chronic obstructive pulmonary disease. History of epilepsy and/or history of psychotic disorder. Patients with history of myasthenia gravis. Patients with diabetes mellitus. Known glucose-6-phosphate dehydrogenase deficiency. Active hepatitis or decompensated cirrhosis. Alanine transaminase or aspartate transaminase increase > 3 fold upper limit of normal (ULN). Patients with creatinine ≥ 1.1 fold ULN. Patients requiring concomitant systemic or inhaled antibiotics (e.g., tobramycin). Known or suspected active tuberculosis or endemic fungal infection. Concomitant immunosuppressive therapy including a long-term (more than 2 weeks) treatment with oral or intravenous glucocorticoids at doses of 20 mg and higher of prednisone daily or an equivalent dose of other glucocorticoids. Patients known to have HIV-positive status or AIDS or known to have other disease that seriously affects the immune system such as active haematological or solid organ malignancy, or splenectomy. History of drug or alcohol abuse. Patients have received quinolones or fluoroquinolones within 14 days before enrollment. Previous enrolment in this study or participation in another study within the previous 4 weeks. Patients with any severe medical condition as determined by medical history that, in the opinion of the investigator, does not allow the patient to carry out all planned procedure of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: All eligible patients will be randomized to receive either treatment with Nemonoxacin or Tavanic® in a ratio of 1:1.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nemonoxacin<br>Nemonoxacin solution for infusion, 500 mg (250 ml), daily, as single intravenous infusion over 90-110 minutes followed by infusion of Placebo (100 ml), solution for infusion, over a minimum duration of 60 minutes. Then will be switched to oral therapy with Nemonoxacin capsules, 500 mg once daily (two 250 mg capsules). | Drug: Nemonoxacin<br>* Solution for infusion, 500 mg (250 ml)<br>Drug: Nemonoxacin<br>* Capsules, 250 mg<br>Drug: Placebo (100 ml)<br>* 0.9% NaCl (100 ml), solution for infusion<br>|
| Active Comparator: Tavanic®<br>Tavanic® solution for infusion, 500 mg (100 ml), daily, as single intravenous infusion over a minimum duration of 60 minutes with previous infusion of Placebo (250 ml), solution for infusion, over 90-110 minutes. Then will be switched to oral therapy with Tavanic®, over-encapsulated film coated tablets, 500 mg once daily (two capsules each containing 250 mg film coated tablet). | Drug: Tavanic<br>* Solution for infusion, 500 mg (100 ml)<br>* Other names: Levofloxacin;Drug: Tavanic<br>* Film coated tablets (each tablet is placed into a capsule shell (overencapsulated) for blinding purposes), 250 mg<br>* Other names: Levofloxacin;Drug: Placebo (250 ml)<br>* 0.9% NaCl (250 ml), solution for infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Clinical Success as Judged by the Investigator | Clinical response is evaluated as clinical success if: all signs and symptoms of pneumonia are resolved or improved with no worsening or appearance of new signs and symptoms of pneumonia; there is no requirement for additional antibiotic therapy; chest roentgenograms (CT scans) are cured or improved | Visit 4 (within 7-9 days after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Clinical Success as Judged by the Investigator | Clinical response is evaluated as clinical success if: all signs and symptoms of pneumonia are resolved or improved with no worsening or appearance of new signs and symptoms of pneumonia; there is no requirement for additional antibiotic therapy | Visit 2(day 4/8 ot treatment), Visit 3 (within 1-2 days after last dose) | 
| Number of Patients With Infection Relapse |  | Visit 5 (within 21-23 days after last dose) | 
| Time to Switch Therapy From Intravenous to Oral Therapy |  | Up to Visit 2 (day 4/8 ot treatment) | 
| Number of Patients Required for Other Antibiotic Treatment |  | Up to 21-23 days after last dose | 
| Number of Patients With Microbiological Success | Microbiological response is evaluated as microbiological success if culture study demonstrates eradication of pathogen or no material available for culture because of clinical success | Visit 2 (day 4/8 ot treatment), 3 (within 1-2 days after last dose), 4 (within 7-9 days after last dose) | 

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