Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease, that causes obstructed airflow from the lungs that causes persistent obstructive airflow limitation.

Acute exacerbation, especially frequent exacerbation, is associated with an increased risk of death in COPD patients. The most common causes of acute attacks are viral and bacterial infections.

This study will assess the efficacy and safety of sitafloxacin, a quinolone antibacterial drug, in participants with AECOPD.

Clinical evidence suggests that AECOPD may be an important factor in the cause of death in patients with COPD. AECOPD typically presents with increased dyspnea, cough, and sputum volume, or purulent changes in sputum. The most common factors of AECOPD are viral and bacterial infections. Anti-infection agents have shown to be effective in patients with infectious AECOPD.

This study will assess the anti-bacterial drug sitafloxacin in participants with AECOPD. Clinical efficacy is the primary objective of the study. Microbiological validity, symptom relief, magnitude of change in symptom score and inflammatory biomarker, and recurrence rate and safety will also be assessed.

Inclusion Criteria:

• Age ≥ 40;
• History of moderate to very severe COPD with a post-bronchodilator Forced Expiratory Volume in One Second/Forced Vital Capacity (FEV1/FVC) < 70% and a post-bronchodilator Forced Expiratory Volume in One Second (FEV1) < 80% of predicted normal value within one year prior to enrollment;
• History of one or more acute exacerbations within one year prior to enrollment;
• At least 6 weeks of stable disease prior to enrollment;
• The acute exacerbation is classified as Anthonisen I (with 3 main symptoms of worsening dyspnea, increased sputum volume and sputum purulence) or II (with sputum purulence and another main symptom);
• Participants can be treated on an outpatient basis after clinical assessment.

Exclusion Criteria:

• Anthonisen III acute exacerbation (Have two major symptoms of worsening dyspnea and increased sputum volume or one of the two major symptoms)
• Hospitalization or intensive care unit (ICU) treatment is required
• Sputum culture within the previous year indicated the presence of pathogenic microorganisms resistant to quinolones
• Quinolone allergy
• History of QTc prolongation, or need for medications to treat QTc prolongation (e.g., Class Ia or Class III antiarrhythmics);
• Definite pulmonary disease other than COPD (asthma, bronchiectasis, active pulmonary tuberculosis, pulmonary embolism, pulmonary fibrosis, lung cancer)
• History of severe cardiovascular disease (e.g., congestive heart failure, clinically significant coronary heart disease, stroke, myocardial infarction and/or stroke within 6 months, clinically significant arrhythmia, previous history of aortic aneurysm or aortic dissection, positive family history, or risk factors (e.g., Marfan syndrome), poorly controlled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg on 2 or more consecutive measurements)
• Severe systemic diseases, such as severe dizziness, headache and other nervous system diseases
• Malignant tumor
• Concomitant or history of tendon disease or myasthenia gravis or Parkinson's disease
• Abnormal liver function, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) level > 3 times the upper limit of normal, and/or total bilirubin level >2 times the upper limit of normal
• With moderate or severe decline of renal function, endogenous creatinine clearance rate (Ccr) < 50ml/min
• History of seizure, or psychiatric condition that could affect compliance with the protocol, or risk for suicide, or history of alcohol or illicit drug abuse
• Immunocompromised participants using glucocorticoids (total dose equivalent to prednisone 20 mg daily for more than 2 weeks) or immunosuppressive agents or HIV infected participants
• Gastrointestinal disorders that may affect drug absorption (e.g., active Crohn's disease, active ulcerative colitis)
• Pregnant or lactating women or women of childbearing potential who are planning to become pregnant
• Participation in other clinical trials within 3 months prior to screening
• Used antibiotics (including systemic and inhalation) 30 days before enrollment
• Serum potassium < 3.5mmol/L at screening, or repeated hypokalemia that was difficult to correct in the past
• Other reasons that the investigator considered inappropriate to participate in the study.

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.