Evaluation of PAN-90806 Eye Drops in Healthy Subjects

The goal of this Phase Ia clinical trial is to evaluate the safety, tolerability, and systemic pharmacokinetics of PAN-90806 eye drops in healthy adult volunteers. The study is designed to determine whether PAN-90806 eye drops can be administered safely in healthy participants and to describe how the drug is absorbed into the bloodstream after repeated ocular dosing. It will also assess what adverse events or other medical problems may occur during treatment.

The main questions this study aims to answer are:

Is PAN-90806 eye drops safe and well tolerated in healthy adult participants? What systemic pharmacokinetic characteristics does PAN-90806 show after administration as an eye drop? What eye-related or systemic adverse events occur during treatment with PAN-90806? Researchers will compare PAN-90806 eye drops with a placebo eye drop formulation that does not contain PAN-90806 but is otherwise identical in composition. This comparison will help evaluate the safety, tolerability, and systemic exposure profile of PAN-90806 under controlled conditions.

This is a randomized, double-blind, placebo-controlled, single-center Phase Ia study. A total of 20 healthy volunteers are planned for enrollment, with participants randomized in a 3:1 ratio to receive either PAN-90806 eye drops (10 mg/mL, 1.0%) or placebo eye drops. Both male and female participants may be enrolled. The study includes 4 visits: a screening visit from Day -14 to Day -1, an admission visit on Day 0, an inpatient dosing period from Day 1 to Day 8, and a discharge visit on Day 9. The total study duration for each participant is approximately 11 to 24 days.

Participants will:

Receive PAN-90806 eye drops or placebo eye drops once daily in both eyes, with 1 drop per eye, on Day 1 and on Days 3 through 7, for a total of 6 dosing days Be admitted to the clinical research unit and remain under inpatient observation during the treatment period Have all doses administered by study staff; self-administration will not be allowed Use single-dose preservative-free study medication containers, which will be discarded immediately after use Follow study restrictions during inpatient stay, including controlled meals, no smoking, no alcohol, no nicotine-containing products, no caffeine-containing foods or drinks, and no strenuous exercise Undergo intensive blood sampling for systemic pharmacokinetic assessment, with a total of 31 blood collection time points and approximately 155 mL of blood collected Complete ophthalmic and general safety assessments, including corneal endothelial cell examination, central corneal thickness, fluorescein corneal staining, lissamine green conjunctival staining, best corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, non-mydriatic fundus photography, laboratory tests, vital signs, physical examinations, ECGs, and adverse event monitoring The pharmacokinetic endpoints include Tmax, Cmax, AUC0-t, t1/2, Cmax,ss, AUCss, CL or CL/F, and DF. Safety and tolerability will be assessed through ocular examinations, laboratory evaluations, vital signs, ECGs, physical examinations, and the incidence and severity of ocular and systemic adverse events, including events of special interest.

Eligible participants must be healthy adults 18 to 50 years of age who meet specified body weight, BMI, ocular health, and general health requirements. Participants with clinically significant eye disease, recent surgery, relevant medical conditions, recent medication use, positive infectious disease screening, substance abuse, or other factors that may interfere with study safety or pharmacokinetic evaluation will be excluded.

Overall, this study is intended to provide an early clinical assessment of PAN-90806 eye drops in healthy volunteers by characterizing their safety profile and systemic pharmacokinetics after repeated bilateral ocular dosing under closely monitored inpatient conditions.

**Inclusion Criteria:**

• Aged 18 to 50 years, inclusive; male or female.
• Body weight: males ≥50.0 kg, females ≥45.0 kg; body mass index (BMI) between 19.0 and 25.0 kg/m², inclusive.
• At screening, in the investigator's judgment, the volunteer is in good health, with normal results or abnormal results without clinical significance for laboratory tests (hematology, blood chemistry, urinalysis), physical examination, vital signs, and ECG.
• At screening, best-corrected visual acuity in either eye must be ≥0.8 (decimal notation using the national standard logarithmic visual acuity chart).
• At screening, in the investigator's judgment, findings in either eye for intraocular pressure, slit-lamp examination, corneal endothelial cell examination, central corneal thickness examination, and non-mydriatic fundus photography are normal or abnormal without clinical significance; and both NEI corneal and conjunctival scores are ≤3.
• Healthy volunteers (including women of childbearing potential and male healthy volunteers) must have no pregnancy plan during the trial and within 28 days after the end of the trial, and must voluntarily use effective contraception.
• Healthy volunteers fully understand the study content, voluntarily participate and sign the informed consent form, and are willing to cooperate with completion of all study procedures.

**Exclusion Criteria:**

• Women of childbearing potential who are pregnant or lactating; or a positive blood pregnancy test at screening (for women of childbearing potential only).
• Active ocular inflammation or infection in either eye at screening.
• History of intraocular surgery in either eye, or history of ocular laser surgery.
• Wearing or planning to wear corneal or scleral contact lenses within 14 days before screening or during the study period.
• At screening, in the investigator's judgment, any clinically significant disease or relevant medical history involving the eyes, immune system, cardiovascular system, kidneys, liver, respiratory system, metabolism, gastrointestinal system, endocrine system, blood, skin, sexually transmitted diseases, musculoskeletal system, nervous system, or psychiatric system that may affect the safety, tolerability, or systemic pharmacokinetic results of this trial.
• Any symptoms of respiratory tract infection within 14 days before screening (such as fever, sore throat, headache, runny nose, etc.).
• Use of any systemic (injectable or oral) or local (skin, eye, ear, or nose) medication within 28 days before screening or planned use during the study period, including over-the-counter cold or flu medications; however, local medications judged by the investigator not to affect the safety, tolerability, or systemic pharmacokinetic results of the trial are allowed as exceptions (such as artificial tears used outside the study period).
• Participation in another drug or medical device clinical trial within 90 days before screening or planned participation during the study period.
• Vaccination within 30 days before screening or planned vaccination during the study period.
• Blood donation or blood loss exceeding 200 mL within 90 days before screening.
• Any history of drug allergy, or known allergy at screening to any component of the investigational product or auxiliary medications required for study procedures.
• Positive result for any of the four virology screening tests at screening (hepatitis B surface antigen, hepatitis C antibody, Treponema pallidum antibody, human immunodeficiency virus antibody).
• Known drug abuse at screening, or a positive urine drug test (morphine, methamphetamine, ketamine).
• Average daily smoking or use of other nicotine-containing products more than 5 times per day within 90 days before screening (such as snuff, nicotine patches, nicotine gum, e-cigarettes, or nicotine inhalers).
• Average daily alcohol intake of more than 2 units within 90 days before screening (1 unit = 10 mL ethanol, equivalent to 200 mL beer at 5% alcohol, 25 mL spirits at 40% alcohol, or 83 mL wine at 12% alcohol).
• Average daily consumption of more than 8 cups of tea, milk tea, coffee, or caffeinated beverages within 90 days before screening (1 cup = 250 mL).
• During admission to the clinical trial ward, inability to comply with the standardized light and moderate diet, smoking cessation (including e-cigarettes), alcohol abstinence, avoidance of any food or beverages containing alcohol, nicotine, or caffeine (such as nicotine gum, coffee, tea, milk tea, chocolate, cola, etc.), and avoidance of strenuous exercise.