A Phase I Study to the Safety, Tolerability, and Pharmacokinetic Characteristics of Felbinac Trometamol Eye Drops of Single-dose and Multiple-dose in Healthy Subjects
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Ophthalmic examination results in single-dose study
研究概览
简要总结
To evaluate the safety and tolerability of felbinac trometamol eye drops of single-dose, multiple-dose, dose escalation in healthy subjects, for providing the basis for the dose setting in the later clinical study.
详细描述
In the single-center, randomized, double-blind, placebo-controlled, single-dose dose escalation study, 48 healthy volunteers will be divided from low dose to high dose into 5 single-dose groups of 0.025%, 0.05%, 0.1%, 0.2% and 0.3%, with both male and female subjects in each group. The study was designed as double-blind, all the single-dose groups containing 10 subjects except the single-dose group of 0.025% containing 8 subjects，and with 2 placebo controls in each group.
Pharmacokinetics blood sampling in different dose groups was designed from low dose to high dose into 4 single-dose groups of 0.05%, 0.1%, 0.2% and 0.3%.
In the single-center, randomized, double-blind, placebo-controlled, multiple-dose dose escalation study, 20 healthy volunteers will be divided into low dose and high dose groups of 0.1% and 0.2%, with both male and female subjects in each group. The study was designed as double-blind, all the dose groups containing 8 subjects and 2 placebo controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 to 45 years old, male or female;
- •Weight: Male subjects should not be less than 50.0kg and female subjects should not be less than 45.0kg, BMI within the range of 19.0 and 26.0 kg/m2(Including the threshold);
- •Eyes corrected visual acuity should be ≥ 1.0 in both eyes and intraocular pressure, slit lamp and fundus examination were normal or abnormality with no clinical significance;
- •The female subjects should be guaranteed to take effective contraception before selected in within a month prior，and all the subjects Regardless of the gender are willing to take effective contraception and no pregnancy is planned for the next 6 months;
- •Volunteer to participate in the study and sign informed consent.
排除标准
- •With ocular diseases, including a history of inner eye surgery or laser surgery;
- •Subjects who had worn contact lenses within 2 weeks prior screening or need to wear it during the study;
- •Subjects who had taken any medicine including Eye ophthalmic drug within 2 weeks prior screening；
- •Subjects with a history of central nervous, mental, cardiovascular, renal, liver, respiratory, metabolic and musculoskeletal systems;
- •Subjects'pretest physical examination, vital signs, ELECTRO cardiogram, laboratory examination and investigator's determination of abnormality with clinical significance.
- •The results of eight immunological tests(HBsAg、HBsAb、HBEAG、HABEAB、HbcAb、HCVAb、TPPA、HIV-P24 Antigen/antibody) is abnormality with clinical significance.
- •A history of clinically significant allergy, especially drug allergy, allergy to aspirin or other non-steroidal anti-inflammatory drugs or known allergy to the drug component or biphenylacetic acid;
- •The average daily smoking amount in the first 3 months was more than 5 cigarettes;
- •Alcohol dependence is suspected or confirmed, with alcohol intake averaging more than 2 units per day for 3 months (1 unit =10 mL ethanol, i.e. 1 unit =200 mL beer at 5% alcohol or 25 mL spirits at 40% alcohol or 83 mL wines at 12% alcohol) or alcohol tests positive;
- •A history of drug abuse, or positive urine tests for ketamine, morphine, methylamphetamine, dimethylene dioxymethamphetamine, or tetrahydrocannabinic acid;
- •Participation in other the clinical trial within 3 months before;
- •Blood donation or blood loss ≥400 mL within 3 months before;
- •Pregnant or lactating women and those planning to become pregnant;
- •Subjects with a history of needle and blood dizziness or intolerance to venipuncture;
- •The investigator thinks it is not suitable to participate in this study.
研究组 & 干预措施
Test group
Group Ⅰ, give the felbinac trometamol eye drops, 0.025%，1 drop，once. Group Ⅱ, give the felbinac trometamol eye drops, 0.05%，1 drop，once. Group Ⅲ, give the felbinac trometamol eye drops, 0.1%，1 drop，once. Group Ⅳ, give the felbinac trometamol eye drops, 0.2%，1 drop，once. Group Ⅴ, give the felbinac trometamol eye drops, 0.3%，1 drop，once. Multiple Group I, give the felbinac trometamol eye drops, 0.1%，1 drop per time，four times each day, for seven days totally.
Multiple Group II, give the felbinac trometamol eye drops, 0.2%，1 drop per time，four times each day, for seven days totally.
干预措施: Felbinac trometamol eye drop (Drug)
Placebo group
Group Ⅰ, give the placebo eye drops, 0.0%，1 drop，once. Group Ⅱ, give the placebo eye drops, 0.0%，1 drop，once. Group Ⅲ, give the placebo eye drops, 0.0%，1 drop，once. Group Ⅳ, give the placebo eye drops, 0.0%，1 drop，once. Group Ⅴ, give the placebo eye drops, 0.0%，1 drop，once. Multiple Group I, give the placebo eye drops, 0.0%, 1 drop per time, four times each day, for seven days totally.
Multiple Group II, give the placebo eye drops, 0.0%, 1 drop per time, four times each day, for seven days totally.
干预措施: Placebo eye drop (Drug)
结局指标
主要结局
Ophthalmic examination results in single-dose study
时间窗: screening period(from Day-14 to Day-1) , 4 hours ± 20minutes after administration
The change of Fluorescence staining on cornea: screening period (from Day-14 to Day-1), 4 hours ±20 minutes after administration
Ophthalmic examination results in multiple-dose study
时间窗: screening period(from Day-14 to Day-1) , 4 hours ± 20minutes after the last administration
The change of Fluorescence staining on cornea: screening period (from Day-14 to Day-1), 4 hours ±20 minutes after the last administration
Intraocular pressure values in single-dose study
时间窗: screening period(from Day-14 to Day-1) , 24 hours after administration
The change of Intraocular pressure: Screening period (from Day-14 to Day-1), 24 hours after administration
Intraocular pressure values in multiple-dose study
时间窗: screening period(from Day-14 to Day-1) , 48 hours after the last administration
The change of Intraocular pressure: Screening period (from Day-14 to Day-1), 48 hours after the last administration
Visual acuity values in single-dose study
时间窗: screening period(from Day-14 to Day-1) , 24 hours after administration
The change of visual acuity: Screening period (from Day-14 to Day-1), 24 hours after administration
Adverse events (AEs) in single-dose study
时间窗: All adverse events are collected from the signing of written informed consent up to 24 hours after drug administration.
The incidence of adverse reactions
Serious adverse events (SAEs) in single-dose study
时间窗: All serious adverse events are collected from the signing of written informed consent up to 24 hours after drug administration.
All serious adverse events that occur during the clinical study
Visual acuity values in multiple-dose study
时间窗: screening period(from Day-14 to Day-1) , 48 hours after the last administration
The change of visual acuity: Screening period (from Day-14 to Day-1), 48 hours after the last administration
Adverse events (AEs) in multiple-dose study
时间窗: All adverse events are collected from the signing of written informed consent up to 72 hours after the last drug administration.
The incidence of adverse reactions
Serious adverse events (SAEs) in multiple-dose study
时间窗: All serious adverse events are collected from the signing of written informed consent up to 72 hours after the last drug administration.
All serious adverse events that occur during the clinical study
次要结局
- AUCss0-t in multiple-dose study(0 hour before the last administration (within 15 minutes) and"10 minutes"，"20 minutes","30 minutes","45 minutes","1 hour ","1.5 hours","2 hours","3 hours","4 hours","6 hours","8 hours","12 hours"and "24 hours"after the last dose (steady state))
- Cmax in multiple-dose study(0 hour before the last administration (within 15 minutes) and"10 minutes"，"20 minutes","30 minutes","45 minutes","1 hour ","1.5 hours","2 hours","3 hours","4 hours","6 hours","8 hours","12 hours"and "24 hours"after the last dose (steady state))
- AUC0-t in single-dose study(0 hour before administration (within 60 minutes before administration) and"10 minutes"，"20 minutes","30 minutes","45 minutes","1 hour ","1.5 hours","2 hours","3 hours","4 hours","6 hours","8 hours","12 hours"and "24 hours"after administration)
- Cmax in single-dose study(0 hour before administration (within 60 minutes before administration) and"10 minutes"，"20 minutes","30 minutes","45 minutes","1 hour ","1.5 hours","2 hours","3 hours","4 hours","6 hours","8 hours","12 hours"and "24 hours"after administration)