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

Hengrui Medicine

Status and phase: Enrolling; Phase 1

Conditions: COPD

Treatments: Drug: HRS-9821 Powder for Inhalation.; Drug: Moxifloxacin Hydrochloride Tablets; Drug: HRS-9821 Powder for Inhalation placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07116915

HRS-9821-I-102

Details and patient eligibility

About

The aim of this study was to evaluate the safety and tolerability of HRS-9821 Powder for Inhalationadministered in a single dose in healthy individuals and multiple doses in patients with COPD。

Enrollment: 82 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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82 participants in 3 patient groups, including a placebo group

HRS-9821 Powder for Inhalation

Experimental group

Description:

Participants inhaled HRS-9821 powder either as a single dose or for 12 days.

Treatment:

Drug: HRS-9821 Powder for Inhalation.

HRS-9821 Powder for Inhalation placebo

Placebo Comparator group

Description:

Participants received a single dose or 12 consecutive days of inhaled powdered placebo with HRS-9821.

Treatment:

Drug: HRS-9821 Powder for Inhalation placebo

Moxifloxacin

Active Comparator group

Description:

Moxifloxacin is oral

Treatment:

Drug: Moxifloxacin Hydrochloride Tablets