A Single- and Multiple- Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SYH2059 Powder for Inhalation

A Phase I, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple- Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SYH2059 Powder for Inhalation in Healthy Participants

Randomized, double-blind and placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetic characteristics of SYH2059 powder for inhalation after single and multiple doses in healthy subjects. The study is composed of 2 parts. Part 1 is to assess the safety, tolerability and pharmacokinetics of a single ascending dose of SYH2059 powder for inhalation. Part 2 is to assess the safety, tolerability and pharmacokinetics of a multiple ascending dose of SYH2059 powder for inhalation.

Inclusion Criteria:

• 1) Adults aged 18 ~ 55 years (inclusive), male or female;
• 2) Body weight ≥ 45.0 kg (female) or ≥ 50.0 kg (male), body mass index (BMI) in the range of 19.0 ~ 28.0 kg/m^2 (inclusive);
• 3) Participant has not engaged in unprotected sexual intercourse within 14 days before screening, and participant and their partner agree to use effective non-hormonal contraception (such as condoms, inert intrauterine devices, female barrier method (cervical cap or diaphragm with spermicide), vaginal contraceptive ring, etc.) or have already adopted permanent contraception measures (such as bilateral tubal ligation, vasectomy, etc.) from signing the ICF to 6 months after the end of the study; No sperm donation plan for male participants from signing the ICF to 6 months after the end of the study, and no egg donation plan for female participants from signing the ICF to 6 months after the end of the study;
• 4) Fully understand the purpose and requirements of this trial, voluntarily participate in the clinical trial and sign the written ICF and can comply with the trial procedures.

Exclusion Criteria:

• 1) History of neurological/psychiatric system, respiratory, endocrine, hematological, musculoskeletal, gastrointestinal, and cardiovascular diseases; hepatic and renal diseases, thymic disorders or other diseases that may affect the study results;
• 2) History of severe drug and food allergies, including allergy to the product or its components; history of herpes zoster infection;
• 3) Pulmonary ventilation function test showing FEV1 measured value/predicted FEV1 ≤ 80% or FVC ≤ 80% of predicted value, or clinically significant;
• 4) History of COPD or other respiratory diseases, such as active or inactive tuberculosis infection, α-1 antitrypsin deficiency, cystic fibrosis, overt asthma, positive bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, pulmonary edema, or interstitial lung disease;
• 5) Individuals currently suffering from oral lesions or oral ulcers;
• 6) Individuals engaged in high-risk occupations or fine work (such as high-altitude workers, pilots, etc.);
• 7) Participants who have taken any prescription drugs, over-the-counter drugs, Chinese patent medicines, herbal medicines, vitamin dietary supplements, or health products (especially CYP enzyme or transporter inhibitors or inducers) within 4 weeks before randomization; or participants using oral long-acting contraceptives or embedded long-acting contraceptives;
• 8) Participants with diseases affecting drug absorption, distribution, metabolism and excretion (such as acute and chronic diarrhea, acute and chronic gastritis, gastrectomy, cholecystectomy, intestinal resection, etc., except appendectomy) as judged by the investigator;
• 9) Participants who cannot receive oral activated charcoal or are allergic to activated charcoal (only 4 mg dose group, tentative);
• 10) Participants with irregular defecation（only 4 mg dose group, tentative）;
• 11) Participants who have undergone any surgical operation within 6 months before signing the ICF;
• 12) Participants with a history of systemic acute infection within 2 weeks before signing the ICF;
• 13) Participants who plan to undergo surgery (including cosmetic surgery, dental surgery and oral surgery) during the trial, or those who plan to participate in strenuous exercise (including body contact sports or collision sports) during the trial;
• 14) Participants who have received any live vaccine (except influenza vaccine) within 28 days prior to screening or plan to receive vaccination during the study;
• 15) Participants who have received any investigational drug or participated in any drug clinical trial within 3 months prior to screening, or participated in other medical research activities, and are judged by the investigator to experience discomfort unsuitable for participation in this study;
• 16) Participants whose physical examination, vital signs measurement, laboratory tests (hematology, urinalysis, stool routine, blood biochemistry, coagulation function, etc.), Chest X-ray (PA & LAT) and abdominal B-ultrasound examination during the screening are judged by the study doctor to be abnormal and clinically significant ;
• 17) Participants with clinically significant ECG abnormalities, QTcF interval ≥ 450 ms (male) or ≥ 470 ms (female), complete left bundle branch block, ST-T interval changes indicating myocardial ischemia, second- or third-degree conduction block, severe bradyarrhythmia or tachyarrhythmia, or history of prolonged QTcF interval;
• 18) Participants who have experienced blood loss or blood donation exceeding 400 mL, received transfusions or use of blood products within 3 months prior to signing the ICF;
• 19) Participants with special dietary requirements who cannot adhere to the standard study diet;
• 20) Subjects with a history of needle syncope, motion sickness or those who cannot tolerate intravenous paracentesis for blood collection;
• 21) Alcoholics: regular drinkers (more than 14 units per week for women and more than 21 units per week for men, such as 360mL beer or 45mL 40% spirits or 150mL wine) in the 6 months prior to signing the ICF, or unable to abstain from alcohol during the study, or a positive alcohol breath test (> 0 mg/100 mL);
• 22) Smokers: smoking ≥5 cigarettes per day for 6 months before signing the ICF or a positive smoke test result;
• 23) Habitual intake of excessive xanthine or caffeine-containing foods or beverages, or other foods affecting drug absorption, distribution, metabolism, excretion and other factors within 1 month prior to screening. For example, coffee (more than 1100mL per day), tea (more than 2200 mL per day), cola (more than 2200 mL per day), energy drinks (more than 1100 mL per day), chocolate (more than 510 g per day);
• 24) Participants with a history of drug abuse/drug use, or those who test positive in drug abuse screening (including benzodiazepine, methamphetamine, cocaine, morphine, ketamine, tetrahydrocannabinolic acid);
• 25) Pregnant or breastfeeding women, or those with positive blood pregnancy test result during screening period;
• 26) Participants with hepatitis B surface antigen (HBsAg), hepatitis C antibody (Anti-HCV), syphilis-specific antibody (TPPA) and human immunodeficiency virus antigen antibody (Anti-HIV) positive during the screening period;
• 27) Participants unwilling or unable to correctly use the inhaler to inhale the investigational product according to the inhaler instructions or those who fail in inhaler training;
• 28) Participants with other factors that, in the opinion of the investigator, are not suitable for participation in the clinical trial.