Beclometasone Dipropionate and Formoterol Inhalation Aerosol for Asthma

A Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Phase III Clinical Study Comparing the Efficacy and Safety of Beclometasone Dipropionate and Formoterol Inhalation Aerosol Versus FOSTER® in Patients With Asthma.

A multicenter, randomized, double-blind, active-controlled, parallel-group Phase III clinical study comparing the efficacy and safety of Beclometasone Dipropionate and Formoterol Inhalation Aerosol versus FOSTER® in patients with asthma. The purpose of this study is to compare the efficacy and safety of the Beclomethasone Dipropionate and Formoterol Fumarate inhalation aerosol (manufactured by Lunan Better Pharmaceutical Co., Ltd.) with FOSTER® in the treatment of patients with asthma.

Inclusion Criteria:

1. Male or female aged ≥18 and ≤75 years.

2. Clinically diagnosed with bronchial asthma for at least 3 months at screening (with traceable diagnostic evidence and medical records), and the diagnosis has been confirmed according to the Guidelines for the Prevention and Management of Bronchial Asthma, meeting the following criteria:

   a) Positive objective test for variable airflow limitation (i.e., meeting any one of the following): (i) Positive bronchodilator reversibility test (i.e., an increase in FEV₁ of ≥12% and an absolute increase of ≥200 mL from pre-bronchodilator values after inhalation of a bronchodilator; or an increase in FEV₁ of ≥12% and an absolute increase of ≥200 mL from baseline after 4 weeks of anti-inflammatory therapy with an inhaled corticosteroid, excluding respiratory tract infections); or (ii) Positive bronchial provocation test: commonly using methacholine or histamine as the inhaled provocative agent, with a positive result defined as a ≥20% decrease in FEV₁ after inhalation, indicating airway hyperresponsiveness. (A positive result from any confirmed objective test for variable airflow limitation performed within 1 year prior to signing the ICF is acceptable; if not available, a positive bronchial provocation or bronchodilator reversibility test must be met at screening.) b) Pulmonary function test: FEV₁ ≥40% of predicted value.

3. Within at least 4 weeks prior to signing the ICF, the subject has been on a stable daily dose of an inhaled corticosteroid (ICS) with "as-needed" short-acting β₂-agonist (SABA) use but asthma is not well controlled (ACQ-5 ≥1.00), OR has been on a stable daily dose of an ICS plus a long-acting β₂-agonist (LABA) and asthma is well controlled (ACQ-5 <1.00).

4. Subjects who use SABA or other reliever medications as needed before screening may be enrolled only if the investigator assesses that they can be switched to the unified rescue medication provided in this study.

5. Willing and able to comply with the protocol requirements and the investigator's instructions for pulmonary function tests, and, after training, able to correctly use the pressurized metered-dose inhaler (pMDI), peak flow meter, and complete the diary card records.

6. Willing to voluntarily participate in this study and sign the informed consent form after full informed consent.

Exclusion Criteria:

1. Have intermittent asthma or asthma that occurs only upon occasional exposure to allergens or chemical sensitizers.

2. Have a history of life-threatening asthma (e.g., brittle asthma, admission to the intensive care unit due to an acute asthma exacerbation) within 1 year prior to screening.

3. Have other respiratory system diseases, including but not limited to allergic bronchopulmonary aspergillosis (ABPA), active tuberculosis, pneumonia, pneumothorax, idiopathic pulmonary fibrosis, clinically significant atelectasis, chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia, chronic bronchitis, or other significant pulmonary abnormalities other than asthma (such as cystic fibrosis, bronchiectasis, or alpha-1 antitrypsin deficiency), and are considered by the investigator to be unsuitable for participation in this clinical study.

4. Have a respiratory tract infection of non-viral etiology, sinusitis, or otitis media within 4 weeks prior to screening.

5. Have a history of severe cardiovascular or cerebrovascular diseases, such as congestive heart failure of New York Heart Association (NYHA) class ≥II, unstable angina, coronary heart disease, myocardial infarction, stroke, etc., within 6 months prior to screening; have a prolonged QTc interval (QTc >450 ms for males or >470 ms for females, corrected using Fridericia's formula) or have ECG abnormalities that are assessed by the investigator as clinically significant and requiring pharmacological treatment; or have poorly controlled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg after adequate treatment).

6. Have oral candidiasis identified at screening.

7. Have laboratory test results meeting any of the following criteria: Liver function: alanine aminotransferase (ALT) >2×ULN and/or aspartate aminotransferase (AST) >2×ULN, and total bilirubin (TBIL) >2×ULN; Renal function: serum creatinine >1.5×ULN; Fasting blood glucose >10 mmol/L or glycated hemoglobin (HbA1c) ≥8.0%; Serum potassium <3.5 mmol/L.

8. Have received biological targeted therapy (including anti-IgE monoclonal antibodies such as omalizumab, anti-IL-5 monoclonal antibodies such as mepolizumab, anti-IL-5 receptor monoclonal antibodies such as benralizumab, or anti-IL-4 receptor monoclonal antibodies such as dupilumab) within 5 half-lives prior to entry into the run-in period.

9. Have experienced an asthma exacerbation requiring systemic corticosteroid treatment or have required oral corticosteroid therapy within 4 weeks prior to screening, or have other diseases that require long-term oral or intravenous corticosteroid therapy.

10. Have used beta-blockers (including eye drops), quinidine, disopyramide, procainamide, phenothiazines, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, or any other medications that may prolong the QTc interval and increase the risk of ventricular arrhythmias within 4 weeks prior to screening.

11. Have a history of drug abuse or alcohol abuse within 1 year prior to screening.

12. Are current smokers; have a smoking history of ≥10 pack-years (1 pack = 20 cigarettes); for those with a smoking history of <10 pack-years, they must have stopped smoking for at least 6 months to be eligible for the study.

13. Have received treatment with any other investigational drug or device in another clinical trial within 3 months prior to screening.

14. Have a known intolerance to or contraindication to beta₂-agonists and/or inhaled corticosteroids, or are allergic to any component of the investigational products.

15. Are pregnant or breastfeeding; or are women of childbearing potential, or male subjects with partners of childbearing potential, who do not agree to use medically recognized effective contraceptive measures (such as an intrauterine device or condom) during the study and for 6 months after the last dose of the investigational product.

16. Meet any of the following conditions prior to randomization:

    1. Run-in period compliance <80% or >120%;
    2. Have an asthma exacerbation during the run-in period (including asthma-related serious adverse events, asthma worsening leading to hospitalization or emergency treatment, unscheduled visits resulting in changes in treatment, etc.);
    3. Are considered by the investigator to be unsuitable for randomization.