Binaprofen: Safety, Tolerability and Pharmacokinetics of Felbinac Trometamol Eye Drops
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Felbinac trometamol eye drop
Felbinac trometamol eye drop: 0.025%、0.05%、0.1%、0.2%、0.3%, 1 drop will be instilled as instructed over one day in single-dose study; 0.1%, 0.2%, 1 drop per time, four times each day and for seven days totally in multiple-dose study.
|
| Placebo Comparator: 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. |
Drug: Placebo eye drop
Placebo eye drop: 0.0%, 1 drop will be instilled as instructed over one day in single-dose study; 0.0%, 1 drop per time, four times each day and for seven days totally in multiple-dose study.
|
Outcome Measures
Primary Outcome Measures
- Ophthalmic examination results in single-dose study [0 hours before administration (within 60 minutes before administration), and 1 hour±10 minutes after administration]
The change of ocular symptoms and signs: baseline (within 60 minutes before administration) and 1 hours±10 minutes after administration
- Ophthalmic examination results in multiple-dose study [0 hours before administration (within 60 minutes before first administration in each day), and 1 hour±10 minutes after each administration]
The change of ocular symptoms and signs: baseline (within 60 minutes before the first dose in each day) and 1 hours±10 minutes after each administration
- Ophthalmic examination results in single-dose study [screening period (from Day-14 to Day-1) , 24 hours after administration]
The change of Fundus examination and slit lamp examination: screening period (from Day-14 to Day-1), 24 hours after administration
- Ophthalmic examination results in multiple-dose study [screening period (from Day-14 to Day-1) , 48 hours after the last administration]
The change of Fundus examination and slit lamp examination: screening period (from Day-14 to Day-1), 48 hours after the last administration
- Ophthalmic examination results in single-dose study [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 [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 [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 [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 [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
- Visual acuity values in multiple-dose study [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 single-dose study [All adverse events are collected from the signing of written informed consent up to 24 hours after drug administration.]
The incidence of adverse reactions
- Adverse events (AEs) in multiple-dose study [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 single-dose study [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
- Serious adverse events (SAEs) in multiple-dose study [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
Secondary Outcome Measures
- 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]
the active metabolite biphenylacetic acid in plasma is determined and the pharmacokinetic parameter is calculated.
- 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)]
the active metabolite biphenylacetic acid in plasma is determined and the pharmacokinetic parameter is calculated.
- 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]
the active metabolite biphenylacetic acid in plasma is determined and the pharmacokinetic parameter is calculated.
- 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)]
the active metabolite biphenylacetic acid in plasma is determined and the pharmacokinetic parameter is calculated.
Eligibility Criteria
Criteria
Inclusion Criteria:
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18 to 45 years old, male or female;
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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);
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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;
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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;
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Volunteer to participate in the study and sign informed consent.
Exclusion Criteria:
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With ocular diseases, including a history of inner eye surgery or laser surgery;
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Subjects who had worn contact lenses within 2 weeks prior screening or need to wear it during the study;
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Subjects who had taken any medicine including Eye ophthalmic drug within 2 weeks prior screening；
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Subjects with a history of central nervous, mental, cardiovascular, renal, liver, respiratory, metabolic and musculoskeletal systems;
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Subjects'pretest physical examination, vital signs, ELECTRO cardiogram, laboratory examination and investigator's determination of abnormality with clinical significance.
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The results of eight immunological tests(HBsAg、HBsAb、HBEAG、HABEAB、HbcAb、HCVAb、TPPA、HIV-P24 Antigen/antibody) is abnormality with clinical significance.
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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;
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The average daily smoking amount in the first 3 months was more than 5 cigarettes;
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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;
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A history of drug abuse, or positive urine tests for ketamine, morphine, methylamphetamine, dimethylene dioxymethamphetamine, or tetrahydrocannabinic acid;
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Participation in other the clinical trial within 3 months before;
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Blood donation or blood loss ≥400 mL within 3 months before;
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Pregnant or lactating women and those planning to become pregnant;
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Subjects with a history of needle and blood dizziness or intolerance to venipuncture;
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The investigator thinks it is not suitable to participate in this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tongren Hospital | Beijing | Beijing | China | 100730 |
Sponsors and Collaborators
- Beijing Tongren Hospital
Investigators
- Principal Investigator: Xiuli Zhao, Ph.D., Beijing Tongren Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GZDGZY-BpED-201901