Pharmacokinetics and Bioequivalence Study of Budesonide Inhalation Aerosol in Humans

Clinical Equivalency Study of Two Formulations of Budesonide Inhalation Aerosol

The test formulation of Budesonide Inhalation Aerosol is bioequivalent to the reference formulation in healthy Chinese subjects under fasting conditions.

In a four-period single-dose oropharyngeal inhalation study of the investigational drug, with a washout period of 3 days. After dosing, subjects should thoroughly rinse their mouth with 150 ml of water and spit out the rinse water.

Blood plasma concentrations of budesonide are collected within the specified sampling time for pharmacokinetic parameter analysis. In each period, blood samples are collected at pre-dose 0 h and at 0.03, 0.07, 0.10, 0.13, 0.17, 0.20, 0.25, 0.33, 0.42, 0.50, 0.75, 1, 2, 4, 6, 8, 10, 12, and 16 h post-dose.

Inclusion Criteria:

1. **Age**: Chinese male or female subjects aged 18 to 65 years (inclusive of the boundary values).
2. **Weight**: Males must weigh ≥50.0 kg, and females must weigh ≥45.0 kg. The Body Mass Index (BMI) calculated as \[ \text{BMI} = \frac{\text{weight (kg)}}{\text{height}^2 (\text{m}^2)} \] must be between 19.0 and 26.0 kg/m² (inclusive of the boundary values).
3. **Informed Consent**: Subjects must fully understand the purpose, nature, methods, and potential adverse reactions of the trial and voluntarily sign a written informed consent form.
4. **Communication and Compliance**: Subjects must be able to communicate effectively with the investigator, correctly use the inhaler device after training, and understand and comply with all the requirements of the study.

Exclusion Criteria:

1. **Examination**: Subjects with clinically significant abnormalities in physical examination, vital signs, ECG, chest X-ray, complete blood count, urinalysis, or biochemical blood tests; subjects with serum potassium levels below the lower limit of normal.
2. **Examination**: Subjects with positive test results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus antigen and antibody (HIV), or syphilis antibody.
3. **Examination**: Subjects with a measured FEV1/predicted FEV1 ≤ 80% or FVC ≤ 80% of the predicted value in pulmonary function tests; or subjects whose pulmonary function test results are judged by the investigator to indicate small airway disease.
4. **Inquiry**: Subjects with a history or current diagnosis of chronic or severe diseases of the liver, kidneys, endocrine system, urinary system, digestive system, blood, or lymphatic system.
5. **Inquiry**: Subjects with a history or current diagnosis of chronic or severe respiratory diseases.
6. **Inquiry**: Subjects with a history or current diagnosis of chronic or severe cardiovascular diseases (especially ischemic heart disease, hypertension, aneurysm, paroxysmal tachycardia, etc.).
7. **Inquiry**: Subjects with a history or current diagnosis of chronic or severe nervous system diseases; or subjects with a history of frequent headaches or dizziness, or those who have experienced headaches or dizziness within one week before screening.
8. **Inquiry**: Subjects with a history of allergy to budesonide, its excipients, or other corticosteroid components; or subjects with a known history of allergies to two or more food or environmental substances, or a history of atopic allergic diseases (urticaria, rash, eczematous dermatitis, etc.).
9. **Inquiry**: Subjects with a history or current diagnosis of glaucoma, cataracts, or blurred vision.
10. **Examination**: Subjects with current oral ulcers, pharyngitis, or enlarged tonsils.
11. **Inquiry**: Subjects who consumed excessive amounts of tea, coffee, or caffeine-containing beverages (8 cups or more per day, 1 cup = 250 mL) within three months before screening, or those who do not agree to abstain from these beverages during the trial.
12. **Inquiry**: Subjects who consumed food that may affect drug metabolism (including grapefruit or grapefruit products, dragon fruit, mango, pomelo, etc.) within 48 hours before screening, or those who do not agree to abstain from such food during the trial.
13. **Inquiry**: Subjects with special dietary requirements that prevent adherence to a uniform diet, or those with difficulty swallowing.
14. **Inquiry + Examination**: Subjects who cannot tolerate venipuncture or have a history of fainting due to blood or needles, or those with difficulty in blood collection.
15. **Inquiry**: Subjects who have undergone surgery that the investigator judges may affect drug absorption, distribution, metabolism, or excretion; or those who plan to undergo surgery within four weeks before screening or during the trial.
16. **Inquiry**: Subjects who used any medication (prescription drugs, over-the-counter drugs, health supplements, vaccines, herbal medicines, etc.) within 30 days before screening.
17. **Examination**: Subjects with a positive alcohol breath test result (breath alcohol content > 0.0 mg/100 mL).
18. **Inquiry**: Subjects with a history of alcohol abuse within the past year (consuming ≥14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine) or those who cannot abstain from alcohol during the trial.
19. **Inquiry**: Subjects who smoked ≥5 cigarettes per day within three months before screening or those who cannot quit smoking during the trial.
20. **Examination**: Subjects with a positive urine nicotine test result.
21. **Inquiry + Internet Screening**: Subjects who participated in any drug clinical trial within three months before screening and received medication, or those who plan to participate in other clinical trials during this study.
22. **Inquiry**: Subjects who donated blood or had significant bleeding (more than 400 mL) within three months before screening; or those who plan to donate blood or blood components during the study or within three months after the study ends.
23. **Examination**: Subjects with a positive urine drug abuse screening result.
24. **Inquiry**: Subjects with a history of drug abuse within the past five years.
25. **Inquiry + Examination**: Pregnant or breastfeeding women, or women of childbearing age who had unprotected sexual intercourse with their partners within 14 days before screening.
26. **Inquiry**: Female subjects who used long-acting estrogen or progesterone injections or implants within six months before screening.
27. **Inquiry**: Male subjects (or their partners) or female subjects who plan to conceive or donate sperm or eggs during the entire trial period and within three months after the study ends, and are unwilling to take appropriate contraceptive measures.
28. Subjects with poor compliance.
29. Subjects who may not be able to complete the study for other reasons, or those whom the investigator deems unsuitable for enrollment.