Inhaled HRS-9821 given as single doses to healthy adults and multiple doses to people with COPD

A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics for a Single Dose of HRS-9821 Powder for Inhalation and Inhalation Suspension Administered in Healthy Subjects and Multiple Doses in Patients With COPD.

This will test whether inhaled HRS-9821 is safe and how the body processes it after one dose in healthy adults and after multiple doses in adults with COPD.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Guangdong Hengrui Pharmaceutical Co., Ltd (Industry-sponsored)
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07116915 on ClinicalTrials.gov

What this trial studies

This Phase I interventional trial gives single inhaled doses of HRS-9821 to healthy volunteers and multiple inhaled doses to patients with COPD to measure safety, tolerability, pharmacokinetics, and pharmacodynamics. Participants receive either HRS-9821 powder for inhalation or inhalation suspension, matching placebos, and moxifloxacin is used as a reference/control in relevant safety assessments. The study collects vital signs, ECGs, lung-function measures, and blood samples over scheduled visits to characterize how the drug is absorbed and cleared and to monitor adverse effects. The sponsor is Guangdong Hengrui Pharmaceutical and the study is conducted at West China Hospital, Sichuan University in Chengdu.

Who should consider this trial

Good fit: Adults aged 40–75 with a confirmed COPD diagnosis who meet the study's lung-function, smoking history, and overall health criteria (or healthy adults aged 18–50 for the single-dose arm) are the intended participants.

Not a fit: People with unstable or very severe COPD, recent smokers, major uncontrolled comorbidities, pregnant individuals, or those outside the trial's BMI and age limits are unlikely to qualify or benefit from this early safety-focused testing.

Why it matters

Potential benefit: If successful, it could define a safe inhaled dosing approach for HRS-9821 and enable later trials that may improve COPD symptoms or lung function.

How similar studies have performed: Other early-phase inhaled COPD therapies have proceeded after positive safety and PK results, but HRS-9821 itself is novel and has not yet been shown effective.

Eligibility criteria

Inclusion Criteria:

1. Informed consent was obtained to participate in the trial
2. Body weight ≥45 kg, BMI 18-33 kg/m2 (both ends included)
3. The 12-lead ECG was normal or abnormal but clinically insignificant until randomization
4. Contraception was strict from the time informed consent was signed until 1 month (for subjects receiving HRS-9821/ placebo) or 3 months (for male subjects receiving moxifloxacin) after the last dose
5. All study regulations and procedures were followed and inhalation devices used in the study were used correctly during the study

   The following inclusion criteria apply only to healthy subjects:
6. Vital signs were normal at screening
7. Pulmonary function was normal during screening
8. No smoking or smoking cessation ≥12 months before screening, and previous smoking history \<5 pack-years；
9. Healthy male 18-50 years old The following inclusion criteria apply only to subjects with COPD
10. Male or female, aged 40-75 years;
11. Patients diagnosed with COPD;
12. A post-bronchodilator FEV1 /FVC \< 0.7,40% ≤FEV1 \< 80% of the predicted value,;
13. Smoking history of≥ 10 pack-years;
14. Normal chest X-ray examination results at screening;
15. Supporting discontinuation of COPD-related medications before randomization；

Exclusion Criteria:

1. Mean QTcF ≥ 450 ms at screening；
2. Persons who had donated blood or had massive blood loss (\> 400 ml) within 4 weeks before screening or who were interested in donating blood during the study
3. Receipt of the investigational drug or device within 4 weeks before randomization or less than 5 times the half-life of the drug, whichever was greater;
4. Patients who had difficulty in blood collection or could not tolerate venipuncture in the past, such as dizzy with needles or blood
5. History of malignancy in any organ system
6. Known allergies to salbutamol, study medication, or any excipients in the formulation
7. Known previous infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); Or positive HIV (according to a trial-site SOP), treponema pallidum antibody, HBV surface antigen, or HCV antibody before randomization
8. History of alcohol abuse
9. History of drug abuse and drug dependence in the past 5 years；
10. Positive for alcohol or substance abuse test before randomization
11. During the study, surgery or treatment that might interfere with the conduct of the study was planned；
12. Unable or unwilling to fully adhere to the study protocol
13. Mentally or legally incapacitated
14. There were any other reasons for the subject not to participate in the study in the opinion of the investigator;
15. Use of a strong/moderate potency drug that inhibits or induces the hepatic drug-metabolizing enzyme CYP3A4 14 days before the first dose;
16. Drugs with effects on P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) were anticipated to be used during the study;
17. History of using HRS-9821 suspension;

    The following exclusion criteria apply only to healthy subjects:
18. Have been treated with antibiotics for upper and lower respiratory tract infections within 12 weeks prior to screening;
19. Abnormal laboratory or physical examination results with clinical significance;
20. Positive urine nicotine test before randomization;
21. Have consumed a prescription within 14 days prior to the first dose or over-the-counter drugs within 48 h prior to the first dose; The following exclusion criteria apply only to subjects with COPD
22. History of life-threatening acute exacerbation of COPD (AECOPD), including admission to intensive care unit and/or need for invasive ventilator support;
23. Diagnosed with other respiratory disorders;
24. Pulmonary heart disease, or pulmonary hypertension caused by lung disease and/or hypoxia;
25. History of lung volume reduction surgery, partial lung resection, lung transplantation, and other surgeries that may affect pulmonary function results;
26. History of AECOPD requiring systemic glucocorticoids or antibiotics or hospitalization within 4 weeks prior to screening;
27. Lower respiratory tract infection requiring antibiotic treatment within 4 weeks prior to screening;
28. Requiring oxygen therapy or home non-invasive ventilation;
29. Currently using or plan to use non-selective beta blockers or other drugs with bronchoconstrictive effects during the study;
30. Patients with serious trauma or major surgery within 6 months prior to screening who are still in the recovery period;
31. Abnormal laboratory tests at screening and baseline.

Where this trial is running

Chengdu, Sichuan

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Study coordinator: Huanhuan Huang

Conditions COPD