Clinical trial NCT05400369: A Study to Evaluate the Efficacy and Safety of Sitafloxacin in Adult Subjects With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Official title: A Multicenter, Randomized, Open-Label, Parallel-Controlled Clinical Study to Evaluate the Efficacy and Safety of Sitafloxacin in Adult Subjects With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COPD Exacerbation Acute
Keywords: Chronic obstructive pulmonary disease
Exacerbation
Sitafloxacin
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2022-06-01
Enrollment: 140
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Achieving Clinical Efficacy in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
timeFrame: End of treatment (approximately Day 10 post-dose)
Secondary outcomes:
measure: Number of Participants Achieving Clinical Efficacy in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
timeFrame: 1 month post-dose
measure: Number of Participants Achieving Microbiological Efficacy in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
timeFrame: End of treatment (approximately Day 10 post-dose)
measure: Number of Days With Symptom Relief in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
timeFrame: From the start of treatment up to relief of three main symptoms of AECOPD (worsening dyspnea, increased sputum volume and sputum purulence), up to 1 month post-dose
measure: Change from Baseline in Each Chronic Obstructive Pulmonary Disease Symptom Score in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
timeFrame: End of treatment (approximately Day 10 post-dose)
measure: Change from Baseline in Inflammatory Biomarker C-reactive Protein in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
timeFrame: End of treatment (approximately Day 10 post-dose)
measure: Recurrence Rate of Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease
timeFrame: End of treatment (approximately Day 10 post-dose) up to 1 month post-dose
Other outcomes:
Locations:
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: The Sixth People's Hospital of Chengdu
city: Chengdu
country: China
facility: West China Hospital Sichuan University
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
city: Fuyang
country: China
facility: Fuyang People's Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
city: Maoming
country: China
facility: Gaozhou People's Hospital
city: Peking
country: China
facility: Peking University Shougang Hospital
city: Shanghai
country: China
facility: Huadong Hospital Affiliated To Fudan University
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wuhan
country: China
facility: The Sixth Hospital of Wuhan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
city: Zhangjiakou
country: China
facility: The First Affiliated Hospital of Hebei North University
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Director
role: STUDY_DIRECTOR
References: