Budesonide/Formoterol Inhalation Powder in Adults With Asthma

A Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Budesonide/Formoterol Inhalation Powder in Adults With Asthma

The goal of this clinical trial is to evaluate whether budesonide/formoterol powder for inhalation (II) manufactured by Shanghai New Huanghe Pharmaceutical Co., Ltd. is non-inferior to the active comparator, Symbicort® Turbuhaler® (AstraZeneca), in the treatment of adult bronchial asthma, and to assess its safety profile in this population.

The main questions it aims to answer are:

Does the test product (budesonide/formoterol 160 μg/4.5 μg) show non-inferior efficacy compared to the reference product (Symbicort® Turbuhaler® 160 μg/4.5 μg) in improving lung function, as measured by the change from baseline in trough FEV1 after 42 days of treatment?

What is the safety profile of the test product in adult patients with asthma?

Researchers will compare participants receiving the test product plus placebo of the comparator to those receiving the active comparator plus placebo of the test product, to see if the test product is non-inferior to the reference product in terms of efficacy, with comparable safety.

Participants will:

Be randomized to receive either the test product (budesonide/formoterol 160 μg/4.5 μg, 2 inhalations twice daily) plus placebo of the comparator, or the active comparator (Symbicort® Turbuhaler® 160 μg/4.5 μg, 2 inhalations twice daily) plus placebo of the test product, for 6 weeks of treatment

Perform daily morning and evening PEF measurements and record them, along with rescue medication use and any adverse events, in a diary card

Attend regular clinic visits for pulmonary function tests, ACQ-5 and AQLQ questionnaires, safety assessments (vital signs, physical and oropharyngeal examinations, laboratory tests, and 12-lead ECG), and drug accountability

Inclusion Criteria:

1. Patients who can understand and comply with the study procedures and methods, are willing to strictly follow the protocol to complete the study, and have signed the written informed consent form.

2. Aged 18 to 75 years (inclusive), male or female.

3. Diagnosed with bronchial asthma according to the Chinese Guidelines for the Prevention and Management of Bronchial Asthma (2020 edition), with documented medical records, and currently inadequately controlled asthma (ACQ-5 score ≥ 1.0).

4. Non-smokers, or have quit smoking for at least 1 year (including cigarettes, cigars, pipe tobacco), with a smoking history of ≤ 30 pack-years [smoking index (pack-years) = daily smoking amount (packs) × smoking duration (years), 1 pack = 20 cigarettes].

5. Positive result from any objective test for variable airflow limitation, either:

   1. Positive evidence from tests performed within 1 year prior to screening, including bronchodilator reversibility test, bronchial provocation test, or mean daily PEF diurnal variability > 10% or weekly PEF variability > 20%; or
   2. If no positive test result within 1 year prior to screening, positive bronchodilator reversibility test during screening (FEV1 increase > 12% and absolute increase > 200 mL, 15-30 minutes after inhalation of 400 μg salbutamol), or positive bronchial provocation test.

6. Pre-bronchodilator FEV1 between 45% and 85% of predicted normal value at screening.

7. Patients who agree to have no plans for fertility, sperm or egg donation, and voluntarily use effective physical contraception (including their partners) during the study and for 3 months after the last dose.

Exclusion Criteria:

1. Life-threatening asthma, defined as asthma attack requiring intubation within 1 year prior to screening or during run-in, and/or history of hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncope.

2. Hospitalization due to asthma within 2 months prior to screening.

3. Acute upper or lower respiratory tract bacterial infection requiring systemic antibiotic treatment within 4 weeks prior to screening, which led to a change in asthma treatment or, in the investigator's judgment, would alter the subject's asthma status or affect participation.

4. Known hypersensitivity to any sympathomimetic drug (e.g., formoterol or salbutamol), any corticosteroid therapy, or lactose (excipient of the study drug).

5. Concurrent respiratory diseases other than asthma, including but not limited to active pneumonia, idiopathic pulmonary fibrosis, clinically significant atelectasis, active pulmonary tuberculosis, chronic obstructive pulmonary disease, bronchiectasis, etc., which in the investigator's judgment may place the subject at undue risk or affect the assessment of study results.

6. History of malignancy of any organ system within the past 5 years (except localized basal cell carcinoma of the skin or carcinoma in situ of the cervix), treated or untreated, with or without evidence of local recurrence or metastasis.

7. Concurrent severe cardiovascular disease, including but not limited to:

   1. NYHA Class III-IV cardiac function;
   2. Severe arrhythmia, e.g., QTc ≥ 480 ms;
   3. Myocardial infarction or unstable angina within 6 months prior to screening;
   4. Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg at rest on 2 or more consecutive measurements).

8. Abnormal liver or kidney function, defined as:

   1. ALT > 2 × ULN or AST > 2 × ULN;
   2. SCr > 1.5 × ULN.

9. History of or concurrent hypokalemia, or serum potassium below the lower limit of normal at screening.

10. History of or current treatment for glaucoma or cataracts.

11. Poorly controlled diabetes mellitus (fasting blood glucose > 10 mmol/L or HbA1c ≥ 8.0%).

12. History of drug abuse, substance abuse, or alcoholism within 1 year prior to screening. Alcoholism defined as average daily alcohol consumption exceeding 2 units (1 unit = 360 mL beer, or 45 mL 40% liquor, or 150 mL wine).

13. Current treatment with beta-blockers (including eye drops).

14. Systemic corticosteroid use: within 4 weeks prior to screening or during screening/run-in requiring systemic corticosteroid therapy, or asthma requiring oral corticosteroid treatment.

15. Use of biologic targeted therapies including anti-IgE monoclonal antibodies (e.g., omalizumab), anti-IL-5 monoclonal antibodies (e.g., mepolizumab), anti-IL-5 receptor monoclonal antibodies (e.g., benralizumab), or anti-IL-4 receptor monoclonal antibodies (e.g., dupilumab), currently within 5 half-lives of the drug.

16. Oral examination revealing suspected candidiasis (unless definitively excluded by the investigator).

17. Participation in another clinical trial and receipt of investigational drug within 2 months prior to enrollment.

18. Pregnant or lactating women, or women of childbearing potential with a positive pregnancy test.

19. Concurrent severe underlying diseases that may affect the evaluation of study efficacy or safety, or any condition that, in the investigator's judgment, makes the subject unsuitable for enrollment.