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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Ciprofloxacin (Cipro, BAYQ3939)

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Nagasaki, Japan, 850-8555
  • Nagasaki, Japan, 852-8501
  • Nagasaki, Japan, 852-8511
  • Niigata, Japan, 950-1197
  • Niigata, Japan, 950-2087
  • Niigata, Japan, 951-8520
  • Okayama, Japan, 700-8607
  • Osaka, Japan, 543-0035
  • Aichi
    • Nagakute, Aichi, Japan, 480-1195
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
  • Ishikawa
    • Kahoku-gun, Ishikawa, Japan, 920-0293
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0024
  • Nagasaki
    • Isahaya, Nagasaki, Japan, 854-8501
    • Isahaya, Nagasaki, Japan, 859-0497
    • Sasebo, Nagasaki, Japan, 857-8511
    • Unzen, Nagasaki, Japan, 854-0301
  • Oita
    • Yufu, Oita, Japan, 879-5593
  • Osaka
    • Kishiwada, Osaka, Japan, 596-8501
  • Saga
    • Ureshino, Saga, Japan, 843-0393
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 434-8511

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ciprofloxacin

Drug: Ciprofloxacin (Cipro, BAYQ3939); (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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: March 21, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (Estimate): March 23, 2012

Study Record Updates

• Last Update Posted (Estimate): April 27, 2015
• Last Update Submitted That Met QC Criteria: April 24, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Community Acquired Pneumonia (CAP); Ciprofloxacin; Bacterial pneumonia; Hospital Acquired Pneumonia (HAP); Secondary infection of chronic respiratory disease; 400 mg BID/TID
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin
• Other Study ID Numbers: 15992