A Phase III Study to Evaluate the Safety, Efficacy and Pharmacokinetics/Pharmacodynamics of BAYQ3939 in Patients With Bacterial Pneumonia

Study Overview
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Brief Summary
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The main objective of this study is to investigate the safety, pharmacokinetics (PK) and the relationship between PK and pharmacodynamics (Minimum Inhibitory Concentration [MIC] and Mutant Prevention Concentration [MPC]) of intravenous BAYQ3939 (400 mg BID and 400 mg TID) in hospitalized patients with bacterial pneumonia or secondary infection of chronic respiratory disease with severe disease or a poor response to other antimicrobials. In addition, the efficacy of the ciprofloxacin, in terms of clinical response and microbiological response, will be investigated, but as a secondary endpoint.

Official Title
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A Prospective, Non-randomized, Open-label, Non-controlled, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics/ Pharmacodynamics of BAYQ3939 (400 mg BID and TID) in Hospitalized Patients With Bacterial Pneumonia or Secondary Infection of Chronic Respiratory Disease With Severe Disease or a Poor Response to Other Antimicrobials

Conditions
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Pneumonia

Intervention / Treatment
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* Drug: Ciprofloxacin (Cipro, BAYQ3939)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating females with written informed consent, 20 years of age or older. Within 48 hours prior to the first study drug administration, all patients should have the pathogens identified with appropriate specimens (e.g., sputum, tracheal aspirate, bronchoalveolar lavage [BAL], protected brushing specimen [PBS]), or should have appropriate specimens highly likely to identify the pathogens sampled. (However, the patients with Legionellosis is enrolled when the test of Legionella antigen is positive.) The following severe bacterial pneumonia meeting the diagnostic criteria of pneumonia or secondary infection of chronic respiratory disease Severe pneumonia Community-acquired pneumonia: PORT score III, IV or V Hospital-acquired pneumonia [HAP]-Group B and with a low risk for multidrug-resistant pathogens Patients with [HAP]-Group A whose pathogen is suspected to be Pseudomonas aeruginosa Hospitalized patients with bacterial pneumonia with a poor response to other antimicrobials Note: The patients should be limited to CAP patients with PORT score III, IV or V and HAP patients with-Group A or B who don't respond to or have a poor response to other antimicrobials over 3day's treatment.2 Secondary infection of chronic respiratory disease Patients who are hospitalized for the treatment of secondary infection of chronic respiratory disease Hospitalized patients with secondary infection of chronic respiratory disease with a poor response to other antimicrobials Note: The patients should be limited to secondary infection of chronic respiratory disease patients who don't respond to or have a poor response to other antimicrobials over 3day's treatment. Exclusion Criteria: Creatinine clearance (Ccr) ≤ 30 mL/min or nephrotic syndrome Patient with chronic treatment of immunosuppressive drug Decompensated congestive heart failure Subject who received more than 24 hours of an antibacterial drug for the current infection Patient who requires Intensive Care Unit (ICU) management [In case subjects who don't correspond to the severity for ICU management need to be admitted to ICU due to a circumstance of the site (e.g. shortage of hospital beds), those subjects shall not be excluded] Patients with infections other than pneumonia or secondary infection of chronic pulmonary disease Lung abscess, or empyema Viral, fungal, mycobacterial, or atypical pneumonia as a primary diagnosis Known or suspected bacteremia secondary to Staphylococcus aureus Known causative microorganisms other than indication (microorganisms) of the study drug, or positive in urinary antigen test of Streptococcus pneumonia Infection that necessitates the use of a concomitant antibacterial agent in addition to study medication [excluding subjects with concomitant use of long-term, low-dose macrolide for chronic respiratory diseases, sulbactam sodium/ampicillin sodium (Unasyn-S) and clindamycin (Dalacin-S)] Known bronchial obstruction or a history of post-obstructive pneumonia Known primary lung cancer

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ciprofloxacin<br> | Drug: Ciprofloxacin (Cipro, BAYQ3939)<br>* (1) Community-acquired pneumonia (CAP): 400 mg BID, i.e. every 12 ± 1 hours (For those with Ccr > 60 mL/min, 400 mg TID, i.e. every 8 ± 1 hours may be considered at the discretion of investigators) for 7 to 14 days. 2) Hospital-acquired pneumonia (HAP): For the patient with Ccr > 60 mL/min, 400 mg TID, i.e. every 8 ± 1hours for 7 to 14 days For the patient with 30 ≤Ccr ≤60 mL/min, 400 mg BID, i.e. every 12 ± 1hours for 7 to 14 days 3) Secondary infection of chronic respiratory disease 400 mg BID, i.e. every 12 ± 1 hours (For those with of Ccr > 60 mL/min, 400 mg TID, i.e. every 8 ± 1 hours may be considered at the discretion of investigators) for 7 to 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety variables will be summarized using descriptive statistics based on adverse events collection |  | Up to 30 (±5) days after the end of treatment | 
| AUC (Area under the blood concentration/time curve) |  | Within 0-24 hours and 48-72 hours after the first study drug administration | 
| Cmax (Maximum observed concentration) |  | Within 0-24 hours and 48-72 hours after the first study drug administration | 
| AUC/MIC (Minimum inhibitory concentration) |  | Within 0-24 hours and 48-72 hours after the first study drug administration | 
| Cmax/MIC |  | Within 0-24 hours and 48-72 hours after the first study drug administration | 
| AUC/MPC (Mutant prevention concentration) |  | Within 0-24 hours and 48-72 hours after the first study drug administration | 
| Cmax/MPC |  | Within 0-24 hours and 48-72 hours after the first study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response rate based on resolution of signs and symptoms |  | Up to 13 days after the first study drug administration | 
| Microbiological response rate, assessed as eradication rate based on microbiologically evaluable patients |  | Up to 23 days after the first study drug administration | 
| Test of cure rate based on resolution of signs, symptoms, and the clinical response |  | Up to 23 days after the first study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ciprofloxacin, Bacterial pneumonia, Community Acquired Pneumonia (CAP), Hospital Acquired Pneumonia (HAP), Secondary infection of chronic respiratory disease, 400 mg BID/TID