A Study to Evaluate the Efficacy and Safety of Sitafloxacin in Adult Subjects With Acute Exacerbation of Chronic Obstructive Pulmonary Disease

COPD Exacerbation Acute Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05400369
• Other study ID #: DSCN-GRV AECOPD-CSIS-001
• Status: Recruiting
• Phase: Phase 4
• Start date: August 10, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: Contact for Clinical Trial Information
• Phone: 908-992-6400
• Email: CTRinfo[@]dsi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 268
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COPD Exacerbation Acute
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Sitafloxacin
Oral administration, 50 mg tablets
• Moxifloxacin Hydrochloride
Oral administration, 400 mg tablets

Locations

Country	Name	City	State
China	The Third Xiangya Hospital of Central South University	Changsha
China	The Sixth People's Hospital of Chengdu	Chengdu
China	West China Hospital Sichuan University	Chengdu
China	The First Affiliated Hospital of Dalian Medical University	Dalian
China	Fuyang People's Hospital	Fuyang
China	Nanfang Hospital Southern Medical University	Guangzhou
China	Qilu Hospital of Shandong University	Jinan
China	Gaozhou People's Hospital	Maoming
China	Peking University Shougang Hospital	Peking
China	Huadong Hospital Affiliated To Fudan University	Shanghai
China	Shenzhen People's Hospital	Shenzhen
China	Tianjin Medical University General Hospital	Tianjin
China	The Sixth Hospital of Wuhan	Wuhan
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou
China	The First Affiliated Hospital of Hebei North University	Zhangjiakou
China	Affiliated Hospital of Guangdong Medical University	Zhanjiang
China	Henan Provincial People's Hospital	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Achieving Clinical Efficacy in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease	Clinical efficacy is divided into clinical cure and clinical ineffective. Clinical cure is defined as the three main symptoms of AECOPD (worsening dyspnea, increased sputum volume and sputum purulence) that disappear or return to the baseline level of stable phase at the end of treatment/discontinuation and no additional systemic antibacterial therapy is required for the target indication.; Clinical ineffective is defined as the three main symptoms of AECOPD (worsening dyspnea, increased sputum volume and sputum purulence) that persist or incompletely disappear (do not return to the baseline level of stable phase).	End of treatment (approximately Day 10 post-dose)
Secondary	Number of Participants Achieving Clinical Efficacy in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease	Clinical efficacy is divided into clinical cure and clinical ineffective. Clinical cure is defined as the three main symptoms of AECOPD (worsening dyspnea, increased sputum volume and sputum purulence) that disappear or return to the baseline level of stable phase at the end of treatment/discontinuation and no additional systemic antibacterial therapy is required for the target indication.; Clinical ineffective is defined as the three main symptoms of AECOPD (worsening dyspnea, increased sputum volume and sputum purulence) that persist or incompletely disappear (do not return to the baseline level of stable phase).	1 month post-dose
Secondary	Number of Participants Achieving Microbiological Efficacy in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease	Microbiological efficacy is determined by bacterial clearance: Clearance is defined as specimens from the original infection site after treatment do not culture pathogenic bacteria from the original infection.	End of treatment (approximately Day 10 post-dose)
Secondary	Number of Days With Symptom Relief in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease	The number of days with symptom relief of the three main symptoms of AECOPD (worsening dyspnea, increased sputum volume and sputum purulence) will be assessed.	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
Secondary	Change from Baseline in Each Chronic Obstructive Pulmonary Disease Symptom Score in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease	Chronic obstructive pulmonary disease symptom scores include dyspnea (ranging from 0 [Dyspnea only with strenuous activity] to 4 [Unable to leave home due to severe respiratory distress, or dyspnea when wearing and undressing]), sputum volume (ranging from 0 [no sputum] to 3 [severe]), sputum purulence (ranging from 0 [myxoid sample] to 3 [severe purulent]), cough score (ranging from 0 [no cough] to 3 [severe cough]), fever (ranging from 0 [=37.0°C] to 3 [>38.0°C], and COPD Assessment Test (CAT) (where questions 1-8, range from a score of 0 [no impact] to 5 [severely impacted]. For all assessments, higher scores indicate worse outcome.	End of treatment (approximately Day 10 post-dose)
Secondary	Change from Baseline in Inflammatory Biomarker C-reactive Protein in Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease		End of treatment (approximately Day 10 post-dose)
Secondary	Recurrence Rate of Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease	Recurrence rate is defined as when the clinical outcome of the participant at the end/discontinuation of treatment is determined to be clinically cured, but AECOPD occurs again within 20 days after drug withdrawal due to incomplete anti-infective treatment, the participant develops one or more of the three main symptoms of worsening dyspnea, increased phlegm production, and sputum production, and also has relevant signs of AECOPD, with repeated blood routine, C-reactive protein and other inflammatory indicators, and needs to receive systemic antibacterial drug treatment again, and the pathogenic bacteria belonged to the same strain and serotype as the bacteria originally infected.	End of treatment (approximately Day 10 post-dose) up to 1 month post-dose