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

Обзор

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

Вмешательства

• Препарат HRS-9821 Powder for Inhalation
  HRS-9821 Powder for Inhalation
• Препарат Placebo
  placebo for HRS-9821 Powder Inhalation

Первичные конечные точки

• Change from baseline in the rate of adverse events [Срок оценки: The screening period lasted until 26days after administration]

Вторичные конечные точки (1)

• Plasma drug concentration after administration [Срок оценки: The screening period lasted until 21 days after administration]

Критерии участия

Критерии включения

• Informed consent was obtained to participate in the trial
• Body weight ≥45 kg,and BMI 18-33 kg/m2 (both ends included)
• The 12-lead ECG was normal or abnormal but clinically insignificant until randomization
• 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
• 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:

• Vital signs were normal at screening
• Pulmonary function was normal during screening
• No smoking or smoking cessation ≥12 months before screening, and previous smoking history <5 pack-years；
• Healthy male 18-50 years old

The following inclusion criteria apply only to subjects with COPD

• Male or female, aged 40-75 years;
• Patients diagnosed with COPD;
• A post-bronchodilator FEV1 /FVC < 0.7,40% ≤FEV1 < 80% of the predicted value,;
• Smoking history of≥ 10 pack-years;
• Normal chest X-ray examination results at screening;
• Supporting discontinuation of COPD-related medications before randomization；

Критерии исключения

• Mean QTcF ≥ 450 ms at screening；
• 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
• 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;
• Patients who had difficulty in blood collection or could not tolerate venipuncture in the past, such as dizzy with needles or blood
• History of malignancy in any organ system
• Known allergies to salbutamol, study medication, or any excipients in the formulation
• 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
• History of alcohol abuse
• History of drug abuse and drug dependence in the past 5 years；
• Positive for alcohol or substance abuse test before randomization
• During the study, surgery or treatment that might interfere with the conduct of the study was planned；
• Unable or unwilling to fully adhere to the study protocol
• Mentally or legally incapacitated
• There were any other reasons for the subject not to participate in the study in the opinion of the investigator;
• Use of a strong/moderate potency drug that inhibits or induces the hepatic drug-metabolizing enzyme CYP3A4 14 days before the first dose;
• Drugs with effects on P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) were anticipated to be used during the study;
• History of using HRS-9821 suspension;

The following exclusion criteria apply only to healthy subjects:

• Have been treated with antibiotics for upper and lower respiratory tract infections within 12 weeks prior to screening;
• Abnormal laboratory or physical examination results with clinical significance;
• Positive urine nicotine test before randomization;
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital, Sichuan University — Чэнду

Идентификаторы

NCT: NCT07567872 · HRS-9821-I-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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