Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Acute exacerbation of Chronic obstructive pulmonary disease, Acute Exacerbation, Chronic obstructive pulmonary disease(COPD), Zabofloxacin, Moxifloxacin
Brief summary
The purpose of this study is to Evaluate the Efficacy and Safety Profiles of oral multiple dose of Zabofloxacin Tablet 400 mg.
Detailed description
A Phase 3, Multicenter, Double Blind, Active Controlled, Randomized Study to Evaluate the Efficacy and Safety of Zabofloxacin for Patients with acute bacterial exacerbation of Chronic obstructive pulmonary disease.
Interventions
DRUGZabofloxacin
Zabofloxacin 367mg tablet P.O. once daily for 5days and then Placebo P.O. once daily for 2days
DRUGMoxifloxacin
Moxifloxacin 400mg tablet P.O. once daily for 7days
Sponsors
Chonbuk National University Hospital
Chosun University Hospital
Bundang CHA Hospital
Chungbuk National University
Kangdong Sacred Heart Hospital
Hanyang University
Asan Medical Center
Gachon University Gil Medical Center
The Catholic University of Korea
Konyang University Hospital
KangWon National University Hospital
Gyeongsang National University Hospital
Kyunghee University Medical Center
Korea University Anam Hospital
DongGuk University
Severance Hospital
Yeungnam University Hospital
Ulsan University Hospital
Ewha Womans University Mokdong Hospital
Inje University
Chonnam National University Hospital
Catholic University of Korea Saint Paul's Hospital
Incheon St.Mary's Hospital
Masan Samsung Hospital, South Korea
Konkuk University Medical Center
Keimyung University Dongsan Medical Center
Wonju Severance Christian Hospital
Hallym University Medical Center
Ajou University
Chungnam National University Hospital
Dong Wha Pharmaceutical Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult male or female same or older than age of 40 * Severity of acute exacerbation of Chronic obstructive pulmonary disease(COPD) must suit oral administration treatment * Diagnosed as COPD before receiving written informed consent and outcome measure of spirometry testing confirmed as \[Ratio of Forced Expiratory Volume in 1 second(FEV1) to Forced Vital Capacity(FVC)\](FEV1/FVC) \< 0.7 * Subject showing following signs and symptoms: (i)Purulent Sputum or Sputum level is increased (ii)Difficulty in breathing is increased * Female subjects who might be pregnant must do pregnancy test and results should be negative before randomization is done. She must receive written informed consent form (NOTE: Subject who has used single hormone contraception for pregnancy control or has not been more than 1 year after Tubule ligation and menopause are excluded from the study) * Subject who can agree and sign written informed consent form approved by Institutional Review Board(IRB) before participating in study and follow study requirements
Exclusion criteria
* Subject who administered excess daily dose of antimicrobial/antibiotics in past 72 hours before receiving written consent * Diagnosed to have pneumonia by taking chest X-ray in past 48 hours before receiving written consent * Diagnosed to have infectious diseases or such diseases results in complications before receiving written consent (NOTE: Septic shock, Bronchiectasis, Lung abscess, Pneumonia, Active tuberculosis, Pulmonary malignancy, Cystic fibrosis, Empyema, Asthma) * Have kidney or liver diseases who correspond following criteria: (i) Creatinine Clearance(CCr) \< 50 mL/min (ii) Blood Urea Nitrogen(BUN) ≥ 30 mg/dl (iii) Alanine Aminotransferase(ALT) or Aspartate Aminotransferase(AST) \> 3 x Upper Limit Normal(ULN) (iv) Total bilirubin \> 2 x ULN (v) Alkaline Phosphatase(ALP) \> 2 x ULN. * Organic gastrointestinal disorder having abnormal absorption problem condition in past 6 months before receiving written consent (NOTE: Active Crohn's disease, active ulcerative colitis) * Diagnosed to have neutropenia where absolute neutrophil count is \< 1,000cells/mm3 (NOTE: Even though subject neutrophil count is \< 1,000cells/mm3, if it is acute infection, subject maybe possible to participate) * Chronic Hepatitis B carrier * Have proof that subject is Hepatitis C carrier or have Hepatitis C antibody * Immunodeficiency diseases such as HIV positive, AIDS, Bone marrow transplant or leukemia * Have medical history of hypersensitive reaction to antibiotics of fluoroquinolones * Have medical history of seizure or administration of anti-seizure drug in past 1 year before receiving written consent (NOTE: Epilepsy, Convulsions, Myasthenia gravis) * Medical history of ventricular arrhythmia * Medical history of QTc prolongation or currently administering drug that delays QTc interval (NOTE: QTc prolongation means QTc interval \> 450 msec) * Complex infections or diseases that can effect study assessment or need long-term antibiotic treatment exceeding 7 days * Subject who has participated in Clinical trials or Bioequivalence test in past 30 days before receiving written consent * Clinically significant by observations considered as unsuitable based on medical judgement by investigators where current condition can effect quality of safety or data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response in the Clinical Populations | 10days | Clinical response corresponding clinical cure at Test of Cure visit. Based on the clinical outcomes, the results of assessment were classified into Clinical Cure, Clinical Failure, Relapse and Indeterminate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response in the Clinical Population | 36days | Clinical response corresponding clinical cure at End of Study visit. Based on the clinical outcomes, the results of assessment were classified into Clinical Cure, Clinical Failure, Relapse and Indeterminate. |
| Clinical Cure Rate in the Microbiological Per Protocol(PP) Population | 10days | Clinical response corresponding clinical cure in the microbiological per-protocol population. Microbiological responses were discriminated for the pathogens isolated from the respiratory secretion samples of subjects. |
| Microbiological Response Rate | 10days | Microbiological response rate in the microbiological per protocol(PP) population. Microbiological rate were discriminated for the pathogens isolated from the respiratory secretion samples of subjects. |
| Change in EXACT-PRO Score | 10 days | The outcome measurement is Change in EXACT-PRO score for clinical populations at Test of cure visit. EXACT-PRO means that the questionnaires for Exacerbation of Chronic Pulmonary Disease Tool-Patient Reported Outcome of United BioSource Corporation(UBC) of USA that had been standardized, equipped with reliability and feasibility applicable to various COPD patients groups were used in order to quantitate frequency, severity and duration of acute exacerbation as a tool to measure acute exacerbation of COPD. EXACT-PRO is consisted of 14 questionnaire items were classified into 3 domains, Respiratory Distress Domain, Cough/Sputum Domain, and Chest Symptoms Domain. The Scores of each domain were to be summed into the domain raw summed score or converted into EXACT domain score according to the conversion table. The total score had value in the range from 0 to 100 and higher the value was, severer the respiratory symptoms were in evaluation. |
| Change in CAT Scores | 10 days | The outcome measurement is Change in CAT scores for clinical populations at Test of cure visit. CAT score means that COPD Assessment Test was used as a tool to assess the effects of COPD on physical, mental status and daily life. CAT is consisted of 8 items in total and each question item was scored from 0 point to 5 point. The scores of each question item were summed into the total score, which had values between 0 and 40. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DW224 Zabofloxacin 367mg tablet P.O. once daily for 3 days and then placebo P.O. once daily for 2 days | 175 |
| Avelox Moxifloxacin 400mg tablet P.O. once daily for 7 days | 167 |
| Total | 342 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | DW224 | Avelox | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 78 Participants | 74 Participants | 152 Participants |
| Age, Categorical Between 18 and 65 years | 97 Participants | 93 Participants | 190 Participants |
| Age, Continuous | 67.76 years STANDARD_DEVIATION 7.79 | 68.40 years STANDARD_DEVIATION 8.04 | 68.07 years STANDARD_DEVIATION 7.91 |
| Region of Enrollment Korea, Republic of | 175 participants | 167 participants | 342 participants |
| Sex: Female, Male Female | 22 Participants | 8 Participants | 30 Participants |
| Sex: Female, Male Male | 153 Participants | 159 Participants | 312 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 175 | 16 / 167 |
| serious Total, serious adverse events | 0 / 175 | 0 / 167 |
Outcome results
Primary
Clinical Response in the Clinical Populations
Clinical response corresponding clinical cure at Test of Cure visit. Based on the clinical outcomes, the results of assessment were classified into Clinical Cure, Clinical Failure, Relapse and Indeterminate.
Time frame: 10days
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DW224 | Clinical Response in the Clinical Populations | 86.71 percentage of participants |
| Avelox | Clinical Response in the Clinical Populations | 86.26 percentage of participants |
Secondary
Change in CAT Scores
The outcome measurement is Change in CAT scores for clinical populations at Test of cure visit. CAT score means that COPD Assessment Test was used as a tool to assess the effects of COPD on physical, mental status and daily life. CAT is consisted of 8 items in total and each question item was scored from 0 point to 5 point. The scores of each question item were summed into the total score, which had values between 0 and 40.
Time frame: 10 days
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DW224 | Change in CAT Scores | -4.46 scores on a scale | Standard Deviation 5.88 |
| Avelox | Change in CAT Scores | -2.48 scores on a scale | Standard Deviation 5.96 |
Secondary
Change in EXACT-PRO Score
The outcome measurement is Change in EXACT-PRO score for clinical populations at Test of cure visit. EXACT-PRO means that the questionnaires for Exacerbation of Chronic Pulmonary Disease Tool-Patient Reported Outcome of United BioSource Corporation(UBC) of USA that had been standardized, equipped with reliability and feasibility applicable to various COPD patients groups were used in order to quantitate frequency, severity and duration of acute exacerbation as a tool to measure acute exacerbation of COPD. EXACT-PRO is consisted of 14 questionnaire items were classified into 3 domains, Respiratory Distress Domain, Cough/Sputum Domain, and Chest Symptoms Domain. The Scores of each domain were to be summed into the domain raw summed score or converted into EXACT domain score according to the conversion table. The total score had value in the range from 0 to 100 and higher the value was, severer the respiratory symptoms were in evaluation.
Time frame: 10 days
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DW224 | Change in EXACT-PRO Score | -6.90 scores on a scale | Standard Deviation 9.59 |
| Avelox | Change in EXACT-PRO Score | -4.29 scores on a scale | Standard Deviation 9.72 |
Secondary
Clinical Cure Rate in the Microbiological Per Protocol(PP) Population
Clinical response corresponding clinical cure in the microbiological per-protocol population. Microbiological responses were discriminated for the pathogens isolated from the respiratory secretion samples of subjects.
Time frame: 10days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DW224 | Clinical Cure Rate in the Microbiological Per Protocol(PP) Population | 88.37 Percentage of participants |
| Avelox | Clinical Cure Rate in the Microbiological Per Protocol(PP) Population | 94.87 Percentage of participants |
Secondary
Clinical Response in the Clinical Population
Clinical response corresponding clinical cure at End of Study visit. Based on the clinical outcomes, the results of assessment were classified into Clinical Cure, Clinical Failure, Relapse and Indeterminate.
Time frame: 36days
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DW224 | Clinical Response in the Clinical Population | 76.22 percentage of participants |
| Avelox | Clinical Response in the Clinical Population | 70.99 percentage of participants |
Secondary
Microbiological Response Rate
Microbiological response rate in the microbiological per protocol(PP) population. Microbiological rate were discriminated for the pathogens isolated from the respiratory secretion samples of subjects.
Time frame: 10days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DW224 | Microbiological Response Rate | 67.44 Percentage of participants |
| Avelox | Microbiological Response Rate | 79.49 Percentage of participants |