Lifitegrast Eye Drops in Healthy Subjects：Phase I Study

Pharmacokinetics and Safety Study of Lifitegrast Eye Drops in Healthy Subjects - A Single-Center, Randomized, Double-Blind, Single-Dose, Two-Period Crossover Design Phase I Clinical Trial

This is a single-center, randomized, double-blind, single-dose, two-period crossover Phase I clinical trial designed to:

• Compare the pharmacokinetic (PK) profiles of Lifitegrast Ophthalmic Solution and Xiidra® in plasma and tears following single-dose administration in healthy subjects.
• Evaluate the safety and tolerability of Lifitegrast Ophthalmic Solution in healthy subjects.

A total of 24 healthy subjects will be randomized into two treatment sequences (Group A: T/R; Group B: R/T). The study duration per subject will be approximately 36 days, including:

• Screening Period (Day -21 to Day -1)
• Treatment Periods (Day 1, followed by a 7-day washout period, then Day 8 or early termination)
• Safety Follow-up (Day 15, 7 days after the last dose).

On Day 1 of Cycle 1, one study eye will be selected and designated for all subsequent tear PK sampling. Treatment assignments:

• Group A: Lifitegrast (T) on Day 1, then Xiidra® (R) on Day 8.
• Group B: Xiidra® (R) on Day 1, then Lifitegrast (T) on Day 8. Each subject will receive one drop of the assigned medication (either Lifitegrast or Xiidra®) in each eye from the same single-dose container. Blood and tear samples will be collected per protocol for PK analysis, including parameters such as Cmax, AUC0-∞, AUC0-t, Tmax, T1/2, λz, and AUC_%Extrap. The PK profiles between the two treatments will be compared to evaluate bioequivalence and assess the safety of Lifitegrast Ophthalmic Solution.

Inclusion Criteria:

• Subjects must meet all the following criteria to be eligible:
• Healthy, aged 18-50 (inclusive), all genders.
• Signed informed consent pre-screening; comprehension of study and ability to complete it per protocol.
• BMI 19-27 kg/m² (inclusive); ≥45 kg for females, ≥50 kg for males.
• Bilateral best-corrected visual acuity ≥4.7 (5m, 5-point logMAR).
• No reported eye discomfort/abnormalities 1 month before randomization.
• No history of dry eye disease, as assessed by the investigator.
• No history of ocular inflammation (e.g., allergic conjunctivitis, uveitis) per investigator judgment.
• Use effective contraception during study and 30 days post-last dose:

Females: non-pregnant, non-lactating; premenopausal use approved methods, no egg donation.

Males with fertile partners: vasectomy (≥30 days, no viable sperm) or approved contraception, no sperm donation.

• Non-smoker, remain smoke-free during study.
• No excessive alcohol (>14 units/week) or illicit drug use history; abstain from both during study.

Exclusion Criteria:

• Subjects will be excluded if they meet any of the following:
• History or current diseases/conditions (e.g., circulatory, endocrine disorders) that pose risks or interfere with the study, as judged by the investigator.
• Blood donation or loss >300 mL within 56 days before randomization; no blood donation during the study.
• Allergy to study medications (e.g., lifitegrast, excipients).
• Prior participation in non - placebo lifitegrast clinical trials.
• Clinically significant abnormal test results:

Vital signs: ear temp >37.7℃ or <35.4℃; pulse >100 or <60 bpm; systolic BP ≥150 or <90 mmHg; diastolic BP ≥90 or <50 mmHg.

ECG: QTcF ≥450 ms (male), ≥460 ms (female). Lab tests: abnormal blood/urine, coagulation, infectious markers, drug/alcohol screenings.

Abnormal abdominal ultrasound or eye exams.

• Intraocular/laser eye surgery within 12 months, other eye surgeries within 3 months before screening, or planned eye surgery during the study.
• Use of ophthalmic drugs (incl. artificial tears), anticholinergics, oral/nasal steroids within 1 month before screening or during the study.
• Tobacco/nicotine use within 6 months before randomization.
• Contact lens use within 1 month before randomization or during the study.
• Prescription/OTC/herbal medications within 2 weeks or 5 half - lives (longer) before randomization or during the study.
• Pregnancy, lactation, or positive pregnancy test at screening.
• Participation in drug/device trials within 30 days or 5 half - lives (longer) before screening, or planned participation during the study affecting results.
• Conditions increasing risks, affecting compliance, or deemed unsuitable by the investigator (e.g., needle phobia).