chronic obstructive pulmonary disease
Conditions
Interventions
the experimental group:GRA2405 inhalation powder, specifications:(1) 1.5 mg GRA2405 per capsule
(2) 3 mg GRA2405 per capsule
SAD-1.5mg : single inhalation administration, 1.5 mg/capsule × 1 capsule
SAD-3mg : single inhalation administration, 3 mg/capsule × 1 capsule
SAD-6mg : single inhalation a
the control group(placebo group):GRA2405 inhalation powder placebo formulation
SAD-3mg : single inhalation administration, placebo × 1 capsule
SAD-6mg : single inhalation administration, placebo × 2 c
Sponsors
No. 28, Qiaozhong Middle Road, Liwan District, Guangzhou
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Healthy Trial Participants: 1. Ability to understand and willingness to comply with the clinical trial protocol, and provision of voluntary written informed consent. 2. Age between 18 and 45 years (inclusive) at screening, both male and female participants eligible. 3. At screening: body weight >= 50 kg for males and >= 45 kg for females; body mass index (BMI) within 19.0–26.0 kg/m² (inclusive). Note: BMI = weight (kg) / height² (m²). 4. Generally healthy, or with medical history deemed by the investigator — based on clinical judgment and drug-specific considerations — as not interfering with participation in this clinical study. 5. Demonstrated ability, after proper training, to correctly use the inhalation device and tolerance of inhaled drug administration. 6. For women of childbearing potential and men whose partners are of childbearing potential: commitment to avoid pregnancy from first administration of study drug through 3 months after the last dose, and use of highly effective non-hormonal contraceptive methods (e.g., consistent and correct use of condoms, abstinence, intrauterine device [IUD], or vasectomy with confirmed azoospermia); hormonal contraceptives (e.g., oral contraceptives, contraceptive injections, subdermal implants) are not permitted. Inclusion Criteria for COPD Trial Participants: 1. Age between 40 and 75 years (inclusive), both male and female participants eligible. 2. Diagnosis of COPD according to the Guidelines for the Diagnosis and Management of Chronic Obstructive Pulmonary Disease (2021 Edition), and currently in a stable phase: no moderate-to-severe COPD exacerbations within 4 weeks prior to screening or during the screening period. 3. Current smoker or former smoker with a smoking history of >= 10 pack-years (pack-years = [cigarettes per day ÷ 20] × years of smoking; e-cigarette use is excluded). 4. At screening, bronchodilator test results (after inhalation of 400 µg salbutamol metered-dose inhaler): • Post-bronchodilator FEV1 >= 30% but < 80% of predicted value; • Post-bronchodilator FEV1/FVC < 0.70. 5. In the investigator’s judgment, able to adjust current COPD treatment per protocol requirements. 6. Demonstrated ability, after proper training, to correctly use the inhalation device and tolerance of inhaled drug administration. 7. Voluntary participation and provision of written informed consent. 8. For women of childbearing potential and men whose partners are of childbearing potential: commitment to avoid pregnancy from first administration of study drug through 3 months after the last dose, and use of highly effective non-hormonal contraceptive methods (e.g., consistent and correct use of condoms, abstinence, IUD, or vasectomy with confirmed azoospermia); hormonal contraceptives (e.g., oral contraceptives, contraceptive injections, subdermal implants) are not permitted.
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Healthy Trial Participants: 1. History of hypersensitivity to phosphodiesterase inhibitors or excipients of the investigational drug, or history of allergy to two or more drugs or foods; 2. Clinically significant abnormalities in vital signs, physical examination, laboratory tests, chest X-ray (posteroanterior view), or 12-lead electrocardiogram (ECG) during screening, as judged by the investigator; 3. FEV1/FVC =8 cups/day, where 1 cup = 250 mL) of tea, coffee, or caffeine-containing beverages within the past 6 months prior to screening; or unwillingness or inability to avoid caffeine-rich food/beverages from 3 days before first dosing through study completion; 10. Consumption of grapefruit- or xanthine-rich foods/beverages within 14 days prior to screening, or unwillingness or inability to avoid such foods/beverages from 3 days before first dosing through study completion; 11. Difficulty with venipuncture, intolerance to venous puncture, or needle/phobia-related syncope; 12. Blood donation, transfusion, blood product use, or blood loss >=400 mL within the past 3 months prior to screening; 13. History of alcoholism (i.e., >28 standard units/week for males or >21 standard units/week for females; 1 standard unit = 14 g ethanol, e.g., 360 mL beer, 45 mL 40% spirits, or 150 mL wine); frequent alcohol consumption (>14 standard units/week) within the past 6 months; or positive breath alcohol test on admission day; 14. Smoking >=5 cigarettes/day within the past 3 months prior to screening; positive cotinine test on admission day; or inability to abstain from all tobacco products during the trial; 15. Use of any medication or vaccination within 28 days prior to screening; 16. Participation in another clinical trial and receipt of investigational drug or device within the past 3 months prior to screening; 17. Pregnancy, lactation, or positive pregnancy test during screening; 18. Inability to correctly administer the investigational drug via inhalation after training; 19. Any other condition deemed unsuitable for enrollment by the investigator. Exclusion Criteria for COPD Trial Participants: 1. Recent respiratory illness: hospitalization for COPD or pneumonia within the past 12 weeks, or acute upper/lower respiratory tract infection requiring antibiot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events, including treatment-emergent adverse events (TEAE), treatment-related adverse events (TRAE), and serious adverse events (SAE);Abnormal changes in vital signs, physical examination, 12-lead electrocardiogram (ECG), and laboratory tests (including complete blood count, blood biochemistry, urinalysis, and coagulation function); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters of GRA2405 in plasma following single inhaled administration in healthy trial participants (SAD);Pharmacokinetic parameters of GRA2405 in plasma following single inhaled administration in healthy trial participants (MAD) and chronic obstructive pulmonary disease (COPD) trial participants.;Pharmacokinetic parameters of GRA2405 in plasma following multiple inhaled administrations in healthy trial participants (MAD) and chronic obstructive pulmonary disease (COPD) trial participants;Pharmacodynamic parameters in chronic obstructive pulmonary disease (COPD) trial participants following single and multiple inhaled administrations—time to onset of FEV? improvement after single inhaled administration;Pharmacodynamic parameters in chronic obstructive pulmonary disease (COPD) trial participants following single and multiple inhaled administrations—change from baseline in FEV? at 12h and 24h after single and multiple inhaled administrations;Pharmacodynamic parameters in chronic obstructive pulmonary disease (COPD) trial participants following single and multiple inhaled administrations—change from baseline in the mean FEV? area under the curve (AUC) over 0–6h, 0–12h, and 0–24h after single and multiple inhaled administrations;Pharmacodynamic parameters in chronic obstructive pulmonary disease (COPD) trial participants following single and multiple inhaled administrations — time to peak FEV? and change from baseline in peak FEV? after single and multiple inhaled administrations; | — |
Countries
China
Contacts
Public ContactNanshan Zhong/ Yumin Zhou
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
Outcome results
None listed