Bioequivalence Study of Budesonide/Formoterol Inhalation Powder in Healthy Participants

A Randomized Crossover Bioequivalence Study of Budesonide/Formoterol Inhalation Powder in Healthy Participants Under Fasting Conditions

The goal of this study is to learn if a new formulation of Budesonide/Formoterol Inhalation Powder (160μg/4.5μg), manufactured by Shanghai New Huanghe Pharmaceutical Co., Ltd., works the same as the already approved reference product, Symbicort® Turbuhaler® (160μg/4.5μg), in the body. It will also learn about the safety of the new formulation.

The main questions it aims to answer are:

• How quickly and how much of the study drug gets into the blood after inhalation, compared with the reference product?
• What medical problems do participants have when taking the study drug?

Researchers will compare the new formulation to the reference product (the already approved treatment) to see if they are bioequivalent.

Participants will:

• Be randomly assigned to receive either the new formulation or the reference product in the first period, then switch to the other in the second period
• Take a single dose of 2 inhalations in each period, with a 4-day washout period between doses
• Have 22 blood samples collected over 36 hours after each dose to measure drug levels in the blood
• Visit the clinic for checkups, including vital signs, physical examinations, and laboratory tests
• Be monitored for any side effects throughout the study

Inclusion Criteria:

1. Aged 18 to 45 years (inclusive), both males and females.
2. Female subjects weighing ≥45.0 kg and male subjects weighing ≥50.0 kg, with a body mass index (BMI) between 18.5 and 26.0 kg/m² (inclusive) (BMI = body weight kg / height m²).
3. Subjects agree to have no fertility or sperm/egg donation plans during the study and within 60 days after study completion, and voluntarily adopt one or more non-pharmacological contraceptive measures during the trial (e.g., complete abstinence, contraceptive ring, partner sterilization, etc.).
4. Voluntarily participate in this clinical trial, able to communicate well with the investigator, and have signed written informed consent.

Exclusion Criteria:

1. Known allergy to the study drug (including its excipients) or its analogues, or allergic constitution (allergic to two or more drugs, foods, or pollen), or known allergy to corticosteroid anti-inflammatory drugs.
2. History of respiratory diseases (active or inactive tuberculosis, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, asthma, chronic cough), immune system diseases, cardiovascular diseases, renal diseases, or hepatic diseases.
3. Previous or current mental disorders, such as schizophrenia, delusional disorder, panic disorder, obsessive-compulsive disorder, behavioral volitional disorder, postpartum mental disorder, paranoid mental disorder, and various neuropsychiatric diseases associated with organic lesions, including but not limited to Alzheimer's disease, convulsions, epileptic seizures, suicidal tendencies, etc.
4. Previous or current glaucoma.
5. Respiratory tract infection within 1 month (30 days) prior to the trial; history of bronchospasm.
6. Use of any medication within 1 month (30 days) prior to the trial, including vitamins, herbal medicines, and drugs that inhibit or induce CYP3A4 enzyme activity (e.g., inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; inhibitors: SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines).
7. Major surgery within 3 months (90 days) prior to the trial, or surgery that may significantly affect the in vivo process of the study drug or safety evaluation.
8. Use of an investigational drug within 3 months (90 days) prior to the trial, or plan to participate in other clinical trials during this study.
9. Blood loss/blood donation exceeding 400 mL within 3 months (90 days) prior to the trial (excluding physiological blood loss in females), receipt of blood transfusion or blood products, or plan to donate blood during the trial or within 1 month (30 days) after the trial.
10. Excessive daily consumption of tea, coffee, or caffeinated beverages within 1 month (30 days) prior to the trial (average >8 cups per day, 200 mL per cup).
11. Consumption of any beverages or foods rich in grapefruit or xanthine within 48 hours prior to dosing; consumption of other substances affecting CYP3A4 enzyme metabolism within 48 hours prior to dosing (e.g., grapefruit, starfruit, dragon fruit, etc.).
12. Smoking history within 1 year prior to the trial, or no smoking history within 1 year but previous smoking duration >3 years, or positive nicotine test result.
13. Any history of drug dependence, or positive urine drug screening result.
14. Frequent alcohol consumption within 3 months (90 days) prior to the trial (≥3 times per week, with an average of ≥200 mL of 50° liquor equivalent per session) or inability to abstain from alcohol during the trial.
15. Positive results for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus antibody at screening.
16. Physical examination, vital signs, laboratory tests, 12-lead ECG, or chest X-ray/CT findings at screening judged by the clinician as clinically significant abnormalities.
17. Pulmonary function test: FEV₁ measured/FEV₁ predicted ≤80% or FVC ≤80% of predicted value.
18. Subjects who appear nervous during screening training with the inspiratory flow meter, or who cannot meet the inspiratory flow meter operation requirements after training.
19. Pregnant or lactating women, or positive pregnancy test.
20. Poor forearm venous conditions, difficulty in blood collection, or inability to tolerate venipuncture.
21. Special dietary requirements, or inability to comply with a unified diet, resulting in inability to complete the trial.
22. Other conditions deemed by the investigator as reasons for exclusion.