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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration (Cmax)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Lifitegrast (T) on Day 1, then Xiidra® (R) on Day 8.
干预措施: Xiidra (Drug)
Xiidra® (R) on Day 1, then Lifitegrast (T) on Day 8.
干预措施: Lifitegrast (Drug)
结局指标
主要结局
Peak Plasma Concentration (Cmax)
时间窗: Day 1 & Day 8: Pre-dose, 10, 20, 30, 45 minutes, and 1 hour post-administration.
Evaluated in plasma and tears.
Area Under the Plasma Concentration-Time Curve (AUC0-∞)
时间窗: Day 1 & Day 8: Pre-dose, 10, 20, 30, 45 minutes, and 1 hour post-administration.
Evaluated in plasma and tears.
Area Under the Plasma Concentration-Time Curve (AUC0-t)
时间窗: Day 1 & Day 8: Pre-dose, 10, 20, 30, 45 minutes, and 1 hour post-administration.
Evaluated in plasma and tears.
Time to Peak Plasma Concentration (Tmax)
时间窗: Day 1 & Day 8: Pre-dose, 10, 20, 30, 45 minutes, and 1 hour post-administration.
Assessment: Evaluated in plasma and tears.
5. Terminal Phase Half-Life (T1/2)
时间窗: Day 1 & Day 8: Pre-dose, 10, 20, 30, 45 minutes, and 1 hour post-administration.
Evaluated in plasma and tears
Elimination Rate Constant (λz)
时间窗: Day 1 & Day 8: Pre-dose, 10, 20, 30, 45 minutes, and 1 hour post-administration.
Evaluated in plasma and tears.
Percentage Extrapolated AUC (AUC_%Extrap)
时间窗: Day 1 & Day 8: Pre-dose, 10, 20, 30, 45 minutes, and 1 hour post-administration
Evaluated in plasma and tears.
次要结局
未报告次要终点