chronic obstructive pulmonary disease
Conditions
Interventions
Part A: Single-dose administration of healthy subjects with dose escalation:Part A is a single-center, randomized, placebo-controlled, and positive drug (moxifloxacin) comparison SAD trial among healt
moxifloxacin is open-label. Four dose escalation cohorts are preset: 1.5, 3, 6 (or 4.5) and 12 (or 9) mg. Among them, 12 mg (or 9 mg) is an optional dose, and 1.5 mg and 3 mg do not undergo dose escal
Part B: Multi-dose administration for COPD patients:Part B is a randomized, double-blind, placebo-controlled multicenter trial for COPD patients. One cohort is preset. The dosage will be determined ba
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
40 Years to 75 Years
Inclusion criteria
Inclusion criteria: The participants must meet all of the following criteria to be included in this study: 1. Voluntarily sign the informed consent form to participate in this trial; 2. Weight >= 45 kg, BMI 18 - 33 kg/m^2 (inclusive of both ends); 3. Before screening to randomization, 12-lead ECG is normal or abnormal but without clinical significance; 4. For female participants with reproductive capacity, the serum pregnancy test is negative before randomization; and must be non-lactating. For female participants with reproductive capacity and male participants with non-lactating partners, they must agree to avoid sperm/egg donation from the time of signing the informed consent form until one month after the last administration (for participants receiving HRS-9821/ placebo treatment) or 3 months (for male participants receiving moxifloxacin) and must take corresponding contraceptive measures voluntarily (see Appendix 1); 5. During the study period, they can comply with all study regulations and procedures, and can correctly use the inhalation device used in this study; The following inclusion criteria only apply to healthy participants: 6. Healthy male participants aged 18 - 50 years (inclusive of both ends, as of the time of signing the informed consent form); 7. Before screening to randomization, vital signs meet the following criteria (inclusive of both ends): — Systolic blood pressure 90 - 140 mmHg, — Diastolic blood pressure 50 - 90 mmHg, — Heart rate 50 - 100 beats/min; 8. FEV1 >= 80% predicted value and FEV1/FVC >= 92% predicted value during the screening period; 9. Before screening, no smoking or smoking cessation for >= 12 months, and previous smoking history = 10 pack-years; 14.Before randomization, they can stop using COPD-related oral treatment drugs within 4 weeks, and stop using inhaled long-acting bronchodilators within 2 weeks, as detailed in 6.6.3.
Exclusion criteria
Exclusion criteria: If the subjects meet any of the following criteria, they will not be included in this study: 1. During the screening period, the mean QTc value of three electrocardiograms is greater than 450 ms (QTc interval calculated by the Fridericia formula: QTcF = QT/(RR0.33)); 2. Within the 4 weeks prior to screening, there was blood donation or significant blood loss (more than 400 milliliters), or the subject intended to donate blood during the study period. 3. Within the 4 weeks before randomization or within less than 5 times the half-life of the drug, the subject received the investigational drug or used the investigational medical device, whichever is longer; 4. Previously had difficulty in blood collection or was intolerant to venipuncture, such as fainting or hematemesis; 5. Had a history of malignant tumors in any organ system; 6. Known to be allergic to salbutamol, the investigational drug or any excipient in the formulation; 7. Had a known history of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV); or was positive for HIV (according to the SOP of the trial center), Treponema pallidum antibody, HBV surface antigen, or HCV antibody before randomization; 8. Had a history of heavy alcohol consumption within the 12 weeks prior to screening (with each week of alcohol consumption >= 14 units: 1 unit = 360 mL of beer, or 25 mL of 40% or more alcohol, or 1 cup of wine, 180 mL); 9. Had a history of drug abuse or drug dependence in the past 5 years; 10. Had a positive alcohol or drug abuse test before randomization; 11. Had a surgical plan or a treatment plan that might interfere with the study during the study period; 12. Could not or was unwilling to fully comply with the study protocol; 13. Was mentally or legally incapacitated; 14. The investigator believed that there were any other reasons for the subject to be unsuitable to participate in this study; 15. Used a strong/medium inhibitor or inducer of liver drug-metabolizing enzyme CYP3A4 within 14 days before the first administration (see Appendix 2 List of CYP enzyme inducers/inhibitors, P-gp inhibitors, BCRP inhibitors for details) or used grapefruit or related products within 7 days before the first administration; 16. It is expected that during the study period, drugs that may affect P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) will be used (see Appendix 2 List of CYP enzyme inducers/inhibitors, P-gp inhibitors, BCRP inhibitors for details); 17. Had previously participated in the HRS-9821-I-101 study and received aerosolized inhalation administration of the investigational drug. The following exclusion criteria only apply to healthy subjects: 18. Within the 12 weeks prior to screening, received antibiotic treatment for upper or lower respiratory tract infections, or had a history of respiratory tract infection within the 4 weeks prior to screening; 19. Had clinically significant abnormalities in laboratory or physical examination results; 20. Had a positive nicotine urine test before randomization; 21. Used a prescription or non-prescription medication within 14 days before the first administration or within 48 hours before the first administration. The following exclusion criteria only apply to COPD subjects in Part B: 22. Had a history of life-threatening acute exacerbation of COPD (AECOPD), including admission to the intensive care unit and/or the need for invasive mechanical ventilation (tracheal intubation/ tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| adverse event;vital signs;health checkup;laboratory inspection;12-lead electrocardiogram; | — |
Secondary
| Measure | Time frame |
|---|---|
| plasma concentration;pharmacokinetic parameters;The forced expiratory volume in the first second (FEV1) from 0 to time t;The average value of the change in FEV1 from the baseline;Change in FEV1 peak compared to baseline;FVC; | — |
Countries
China
Contacts
Public ContactWeimin Li/ Zhu Luo
West China Hospital of Sichuan University
Outcome results
None listed