Safety, Tolerability, and Pharmacokinetics of PA9159 Nasal Spray in Healthy Adult Subjects

Inclusion Criteria:

• Male and female subjects aged 18 to 65 years (including upper and lower limits);
• Male body weight ≥ 50 kg, female weight ≥ 45 kg, body mass index (BMI) between 19 and 28 kg/m2 (including cut-off values);
• Voluntary participation and signing of informed consent.

Exclusion Criteria:

• Those with a history or current history of serious diseases such as respiratory,cardiovascular, digestive, endocrine, hematological, immune, psychiatric,neurological, and otologic diseases, with special attention to a history of recurrent (defined as > 1) or disseminated herpes zoster, history of recurrent infections,tuberculosis infection, glaucoma and cataract; Suffering from acute, chronic or localinfectious diseases (e.g., eye, nose infection, etc.);
• Those who are allergic to the study drug or any component of the study drug (refer tothe susceptibility of the body to allergic reactions, or to a variety of food, drugs,or environmental substances);
• Any past or current medical history that may affect the safety of the study in thebody, especially any nasal disorder affecting drug absorption: a) History of long-termnasal congestion, rhinorrhea, nasal pruritus, headache, epistaxis, etc.; b) asthma,aspirin stress response, chronic respiratory disease, etc.; c) History of nasalsurgery, trauma, allergic rhinitis, chronic rhinitis, sinusitis, severe deviation ofnasal septum, etc., and the researchers believe that it is still clinicallysignificant;
• Abnormal and clinically significant vital signs, physical examination, nasalexamination, laboratory tests (hematology, blood chemistry, urinalysis, coagulationfunction, serum cortisol), ECG, etc., during screening;
• Positive test results and have clinical significance for human immunodeficiency virusHIV-P24 antigen/antibody, hepatitis C virus (HCV) antibody, treponema pallidum (TP),or hepatitis B five items (hepatitis B surface antigen, hepatitis B surface antibody,hepatitis B e antigen, hepatitis B e antibody, and hepatitis B core antibody);
• Regular drinkers within 6 months prior to screening,That is, drink more than 14 unitsof alcohol per week (1 unit = 360 mL of beer containing 5% alcohol or 45 mL of spiritswith 40% alcohol or 150 mL of wine with 12% alcohol content) or who have a positivealcohol breath test at screening or who cannot stop alcohol intake during the study;
• Smoking more than 5 cigarettes per day on average within 3 months prior to screening,or unable to discontinue the use of any tobacco products during the trial;
• History of drug abuse, history of drug abuse, or positive urine screening for drugabuse (including morphine, methamphetamine, ketamine, dimethyldioxymethamphetamine,tetrahydrocannabinol acid);
• Those who have taken any drugs (prescription drugs, over-the-counter drugs, Chineseherbal medicines, vaccines) or health products within 2 weeks prior to screening andduring screening;
• Those who have used glucocorticoid-containing preparations or any drugs that affectCYP3A4 enzyme activity (e.g., ritonavir or ketoconazole, etc.) within 30 days prior toscreening and during screening;
• Consumption of beverages or foods containing grapefruit, dragon fruit, mango,grapefruit, pomegranate, papaya, carambola within 14 days prior to screening andduring screening, or who do not agree to stop eating the above-mentioned diet duringthe study;
• Consumption of any caffeine- and xanthine-rich food or beverages (coffee, tea, cola,chocolate, seafood, animal liver, etc.) within 48 hours prior to the first dose ofstudy drug, or who do not agree to stop eating these diets during the study;
• It cannot be guaranteed that effective contraceptive measures or fertility planners orsperm or egg donors are taken during the trial and for at least 1 year after the lastdose;
• Donation or massive blood loss (≥ 300 mL, except during female physiology) or use ofblood products or transfusions within 90 days prior to screening and during screening;
• Participating in other clinical investigators or subjects participating in otherclinical trials within 90 days prior to screening for less than 7 days;
• Major surgery (as judged by the investigator based on past medical history data),major trauma, or planned surgery during the study within 6 months prior to screening;
• Difficulty in venous blood collection, or a known history of multiple needle sicknessand blood sickness;
• Women with a positive pregnancy test or breastfeeding;
• Other conditions that, in the opinion of the investigator, are not suitable forparticipation in the study or the subject is unable to participate in the study due tohis/her own reasons.