Safety and Efficacy Study of Oral Zabofloxacin in Community Acquired Pneumonia
Primary Purpose
Community Acquired Pneumonia
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Zabofloxacin
Levofloxacin 500mg
Zabofloxacin 400mg
Sponsored by
About this trial
This is an interventional treatment trial for Community Acquired Pneumonia focused on measuring pneumonia, Community acquired pneumonia of moderate severity
Eligibility Criteria
Inclusion Criteria:
- Male or female >/= 18 years old
- Documented fever (oral >100°F (37.8°C), tympanic >101°F (38.1°C)must be documented within the time frame of 24 hours prior to first dose through 24 hours after first dose of study drug
- Community-acquired pneumonia of moderate severity (defined as PSI Risk Class II or III) requiring administration of antibiotics
- Dyspnea and/or tachypnea (>20 breaths/minute)
Clinical diagnosis of pneumonia, as demonstrated by all of the following signs and symptoms:
- new or increased cough
- production of purulent sputum or a change in the character of sputum in subjects who normally have purulent sputum
- auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (e.g., bronchial breath sounds, egophony, or dullness on percussion)
- Females must be surgically sterile (e.g., tubal ligation, hysterectomy), post-menopausal at least 2 years, or if of childbearing potential, they must have a negative urine pregnancy test (β-human chorionic gonadotropin [β-hCG]) prior to randomization into the study. Males and females must agree that if they have intercourse that they will use at least two medically accepted methods of birth control (e.g., hormonal contraceptive, intrauterine device, spermicide, or condom) from study entry through 60 days after discontinuation of study drug treatment
- Able to give written informed consent in a manner approved by the Institutional Review Board or Ethics Committee and comply with the requirements of the study
Exclusion Criteria:
Subjects must NOT meet any of the following exclusion criteria:
- Received one or more doses of any systemic antibiotic in the last 2 weeks
- Diagnosed with any other infection requiring systemic antibacterial therapy
- Require long-term (>7 days) antibiotic therapy
- Previous diagnosed condition that might mimic or complicate the course and evaluation of the infectious disease process (e.g., septic shock, bronchiectasis, lung abcess or empyema, aspiration pneumonia, active tuberculosis, pulmonary malignancy, cystic fibrosis, post-obstructive pneumonia, etc.)
- Hypothermia (oral <96°F [35.6°C}, tympanic <97°F [35.9°C]
- Hospitalization (inpatient) in the previous 60 days or infection presumably acquired in the hospital
- Resident of a skilled nursing facility anytime in the previous 60 days or infection presumably acquired in a skilled nursing facility
- Chronic infection with Hepatitis B
- Any evidence of, or is a known carrier of , Hepatitis C antibody
- Infection with Clostridium difficile
- Immunocompromising illness, including known human immunodeficiency virus (HIV) positivity or AIDS, organ (bone marrow) transplant recipients, and hematological malignancy
- Psychotic disease, peripheral neuropathy, and glucose-6-phosphate dehydrogenase deficiency; uncontrolled or poorly controlled diabetes. Diabetic subjects who are stable and on a stable course of antihyperglycemic agents for the past 3 months will be permitted in the trial.
- High exposure to sunlight or ultraviolet radiation
- Immunosuppressive therapy, including cancer chemotherapy or chronic use of corticosteroids (i.e., >20mg prednisone or equivalent per day for >/= 14 days within the last 6 months
History of renal or hepatic disease as defined by at least one of the following:
- Calculated creatinine clearance <50 mL/min (any subject on dialysis must be excluded)
- BUN >/= 30 mg/dL
- ALT or AST > 3x ULN
- Total bilirubin > 2x ULN
- Alkaline phosphatase > 1.25x ULN
- History of or current malabsorption conditions (i.e., short bowel syndrome, active Crohn's disease, celiac disease, etc.)
- Neutropenia as defined by absolute neutrophil count <1000 cells/mm3. Subjects with neutrophil counts as low as 500 cells/mm3 are permitted if the reduction can be documented to be due to the acute infectious process
- Platelet count <75,000/mm3. Subjects with platelet counts as low as 50,000/mm3 are permitted if the reduction is historically stable
- Coagulation tests >1.5x ULN (PT, PTT, or INR). Subjects on anticoagulants with values > 1.5x ULN can be enrolled, provided these values are historically stable and within the therapeutic range
- History of alcohol or drug abuse in the past 2 years
- History of seizure or currently receiving anti-seizure medication anytime in the past year, or a seizure in the past year
- History of ventricular arrhythmia
- History of QTc prolongation (i.e., >450msec) or observed QTc measurement at screening > 450msec, or a history of additional risk factors for Torsade de Pointe, such as heart failure, hypokalemia, or familial history of Long QT syndrome
- Require medications that may prolong the QTc interval
- Require medications that affect absorption, including but not limited to sucralfate or cimetidine
- Require treatment with theophylline, probenecid, vitamin K antagonists (other than warfarin; subjects must be on stable dose of warfarin and within therapeutic range)
- Pregnant, planning to become pregnant, or breast feeding
- Received any investigational drug or device within 30 days prior to study entry
- Previously received zabofloxacin in a clinical trial
- History of allergy or intolerability to fluoroquinolones
- History of fluoroquinolone tendinopathy
- Evidence of immediately life-threatening disease including, but not limited to current or impending respiratory failure, acute heart failure, shock, acute coronary syndrome, unstable arrhythmias, hypertensive emergency, acute hepatic failure, active gastrointestinal bleeding, profound metabolic abnormalities (e.g., diabetic ketoacidosis), or acute cerebrovascular events
- Current condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the data
- Unable or unwilling to adhere to sthe study specified procedures and restrictions
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Levofloxacin 500mg
Zabofloxacin 5 days
Zabofloxacin 3 days
Arm Description
Levofloxacin 500mg once daily for 7 days
Zabofloxacin 400mg for 5 days
Zabofloxacin 400mg for 3 days
Outcomes
Primary Outcome Measures
Safety
Assess safety through monitoring of adverse events, ECGs, and the collection of conventional laboratory data (i.e., chemistry panel, CBC with differential, urinalysis)
Secondary Outcome Measures
Efficacy of the two dosing regimens of zabofloxacin
Determine the clinical response and microbiological response of two dosing regimens in the treatment of bacteriologically confirmed CAP of moderate severity; determine the pharmacokinetic profile in subjects with CAP.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01081964
Brief Title
Safety and Efficacy Study of Oral Zabofloxacin in Community Acquired Pneumonia
Official Title
A Phase 2, Multi-Dose, Double-Blind, Double-Dummy, Active-Control, Randomized Study to Evaluate the Safety, Efficacy and Pharmacokinetic Profile of Two Dosing Regimens of Zabofloxacin for the Treatment of Community-Acquired Pneumonia of Moderate Severity
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Terminated
Why Stopped
Financial considerations
Study Start Date
March 2010 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
June 2012 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IASO Pharma Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
A double-blind, three-arm study, to evaluate the safety and efficacy of two dosing regimens of zabofloxacin (a fluoroquinolone antibiotic) in community acquired pneumonia.
Detailed Description
The study is a Phase 2, global, prospective, multi-dose, double-blind, double-dummy, active-control, randomized, parallel-group, multicenter study of oral zabofloxacin HCl (400mg) versus oral levofloxacin (500mg) in the treatment of adults with community-acquired pneumonia of moderate severity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Community Acquired Pneumonia
Keywords
pneumonia, Community acquired pneumonia of moderate severity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Levofloxacin 500mg
Arm Type
Active Comparator
Arm Description
Levofloxacin 500mg once daily for 7 days
Arm Title
Zabofloxacin 5 days
Arm Type
Experimental
Arm Description
Zabofloxacin 400mg for 5 days
Arm Title
Zabofloxacin 3 days
Arm Type
Experimental
Arm Description
Zabofloxacin 400mg for 3 days
Intervention Type
Drug
Intervention Name(s)
Zabofloxacin
Intervention Description
Zabofloxacin 400mg capsule once daily for 3 days
Intervention Type
Drug
Intervention Name(s)
Levofloxacin 500mg
Intervention Description
Levofloxacin 500mg orally for 7 days
Intervention Type
Drug
Intervention Name(s)
Zabofloxacin 400mg
Intervention Description
Zabofloxacin 400mg orally for 5 days
Primary Outcome Measure Information:
Title
Safety
Description
Assess safety through monitoring of adverse events, ECGs, and the collection of conventional laboratory data (i.e., chemistry panel, CBC with differential, urinalysis)
Time Frame
Up to 35 days after first dose
Secondary Outcome Measure Information:
Title
Efficacy of the two dosing regimens of zabofloxacin
Description
Determine the clinical response and microbiological response of two dosing regimens in the treatment of bacteriologically confirmed CAP of moderate severity; determine the pharmacokinetic profile in subjects with CAP.
Time Frame
Up to 35 days after first dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female >/= 18 years old
Documented fever (oral >100°F (37.8°C), tympanic >101°F (38.1°C)must be documented within the time frame of 24 hours prior to first dose through 24 hours after first dose of study drug
Community-acquired pneumonia of moderate severity (defined as PSI Risk Class II or III) requiring administration of antibiotics
Dyspnea and/or tachypnea (>20 breaths/minute)
Clinical diagnosis of pneumonia, as demonstrated by all of the following signs and symptoms:
new or increased cough
production of purulent sputum or a change in the character of sputum in subjects who normally have purulent sputum
auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (e.g., bronchial breath sounds, egophony, or dullness on percussion)
Females must be surgically sterile (e.g., tubal ligation, hysterectomy), post-menopausal at least 2 years, or if of childbearing potential, they must have a negative urine pregnancy test (β-human chorionic gonadotropin [β-hCG]) prior to randomization into the study. Males and females must agree that if they have intercourse that they will use at least two medically accepted methods of birth control (e.g., hormonal contraceptive, intrauterine device, spermicide, or condom) from study entry through 60 days after discontinuation of study drug treatment
Able to give written informed consent in a manner approved by the Institutional Review Board or Ethics Committee and comply with the requirements of the study
Exclusion Criteria:
Subjects must NOT meet any of the following exclusion criteria:
Received one or more doses of any systemic antibiotic in the last 2 weeks
Diagnosed with any other infection requiring systemic antibacterial therapy
Require long-term (>7 days) antibiotic therapy
Previous diagnosed condition that might mimic or complicate the course and evaluation of the infectious disease process (e.g., septic shock, bronchiectasis, lung abcess or empyema, aspiration pneumonia, active tuberculosis, pulmonary malignancy, cystic fibrosis, post-obstructive pneumonia, etc.)
Hypothermia (oral <96°F [35.6°C}, tympanic <97°F [35.9°C]
Hospitalization (inpatient) in the previous 60 days or infection presumably acquired in the hospital
Resident of a skilled nursing facility anytime in the previous 60 days or infection presumably acquired in a skilled nursing facility
Chronic infection with Hepatitis B
Any evidence of, or is a known carrier of , Hepatitis C antibody
Infection with Clostridium difficile
Immunocompromising illness, including known human immunodeficiency virus (HIV) positivity or AIDS, organ (bone marrow) transplant recipients, and hematological malignancy
Psychotic disease, peripheral neuropathy, and glucose-6-phosphate dehydrogenase deficiency; uncontrolled or poorly controlled diabetes. Diabetic subjects who are stable and on a stable course of antihyperglycemic agents for the past 3 months will be permitted in the trial.
High exposure to sunlight or ultraviolet radiation
Immunosuppressive therapy, including cancer chemotherapy or chronic use of corticosteroids (i.e., >20mg prednisone or equivalent per day for >/= 14 days within the last 6 months
History of renal or hepatic disease as defined by at least one of the following:
Calculated creatinine clearance <50 mL/min (any subject on dialysis must be excluded)
BUN >/= 30 mg/dL
ALT or AST > 3x ULN
Total bilirubin > 2x ULN
Alkaline phosphatase > 1.25x ULN
History of or current malabsorption conditions (i.e., short bowel syndrome, active Crohn's disease, celiac disease, etc.)
Neutropenia as defined by absolute neutrophil count <1000 cells/mm3. Subjects with neutrophil counts as low as 500 cells/mm3 are permitted if the reduction can be documented to be due to the acute infectious process
Platelet count <75,000/mm3. Subjects with platelet counts as low as 50,000/mm3 are permitted if the reduction is historically stable
Coagulation tests >1.5x ULN (PT, PTT, or INR). Subjects on anticoagulants with values > 1.5x ULN can be enrolled, provided these values are historically stable and within the therapeutic range
History of alcohol or drug abuse in the past 2 years
History of seizure or currently receiving anti-seizure medication anytime in the past year, or a seizure in the past year
History of ventricular arrhythmia
History of QTc prolongation (i.e., >450msec) or observed QTc measurement at screening > 450msec, or a history of additional risk factors for Torsade de Pointe, such as heart failure, hypokalemia, or familial history of Long QT syndrome
Require medications that may prolong the QTc interval
Require medications that affect absorption, including but not limited to sucralfate or cimetidine
Require treatment with theophylline, probenecid, vitamin K antagonists (other than warfarin; subjects must be on stable dose of warfarin and within therapeutic range)
Pregnant, planning to become pregnant, or breast feeding
Received any investigational drug or device within 30 days prior to study entry
Previously received zabofloxacin in a clinical trial
History of allergy or intolerability to fluoroquinolones
History of fluoroquinolone tendinopathy
Evidence of immediately life-threatening disease including, but not limited to current or impending respiratory failure, acute heart failure, shock, acute coronary syndrome, unstable arrhythmias, hypertensive emergency, acute hepatic failure, active gastrointestinal bleeding, profound metabolic abnormalities (e.g., diabetic ketoacidosis), or acute cerebrovascular events
Current condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the data
Unable or unwilling to adhere to sthe study specified procedures and restrictions
Facility Information:
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
City
Toney
State/Province
Alabama
ZIP/Postal Code
35773
Country
United States
City
Ft. Myers
State/Province
Florida
ZIP/Postal Code
33916
Country
United States
City
Eagle
State/Province
Idaho
ZIP/Postal Code
93616
Country
United States
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
City
Keego Harbor
State/Province
Michigan
ZIP/Postal Code
48320
Country
United States
City
Belvidere
State/Province
New Jersey
ZIP/Postal Code
078238
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45432
Country
United States
City
Springfield
State/Province
Ohio
ZIP/Postal Code
45504
Country
United States
City
Gresham
State/Province
Oregon
ZIP/Postal Code
97030
Country
United States
City
Warminster
State/Province
Pennsylvania
ZIP/Postal Code
18974
Country
United States
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study of Oral Zabofloxacin in Community Acquired Pneumonia
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