Safety, Tolerability and Pharmacokinetics of Felbinac Trometamol Eye Drops

NCT05085106 | Unknown Phase 1

• 1 other identifier: GZDGZY-BpED-201901
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Eye drop; Safety; Tolerability

Outcome Measures

Primary Outcomes (14)

• Ophthalmic examination results in single-dose study

  The change of ocular symptoms and signs: baseline (within 60 minutes before administration) and 1 hours±10 minutes after administration

  0 hours before administration (within 60 minutes before administration), and 1 hour±10 minutes after administration

• Ophthalmic examination results in multiple-dose study

  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

  0 hours before administration (within 60 minutes before first administration in each day), and 1 hour±10 minutes after each administration

• Ophthalmic examination results in single-dose study

  The change of Fundus examination and slit lamp examination: screening period (from Day-14 to Day-1), 24 hours after administration

  screening period (from Day-14 to Day-1) , 24 hours after administration

• Ophthalmic examination results in multiple-dose study

  The change of Fundus examination and slit lamp examination: screening period (from Day-14 to Day-1), 48 hours after the last administration

  screening period (from Day-14 to Day-1) , 48 hours after the last administration

• Ophthalmic examination results in single-dose study

  The change of Fluorescence staining on cornea: screening period (from Day-14 to Day-1), 4 hours ±20 minutes after administration

  screening period(from Day-14 to Day-1) , 4 hours ± 20minutes after administration

• Ophthalmic examination results in multiple-dose study

  The change of Fluorescence staining on cornea: screening period (from Day-14 to Day-1), 4 hours ±20 minutes after the last administration

  screening period(from Day-14 to Day-1) , 4 hours ± 20minutes after the last administration

• Intraocular pressure values in single-dose study

  The change of Intraocular pressure: Screening period (from Day-14 to Day-1), 24 hours after administration

  screening period(from Day-14 to Day-1) , 24 hours after administration

• Intraocular pressure values in multiple-dose study

  The change of Intraocular pressure: Screening period (from Day-14 to Day-1), 48 hours after the last administration

  screening period(from Day-14 to Day-1) , 48 hours after the last administration

• Visual acuity values in single-dose study

  The change of visual acuity: Screening period (from Day-14 to Day-1), 24 hours after administration

  screening period(from Day-14 to Day-1) , 24 hours after administration

• Visual acuity values in multiple-dose study

  The change of visual acuity: Screening period (from Day-14 to Day-1), 48 hours after the last administration

  screening period(from Day-14 to Day-1) , 48 hours after the last administration

• Adverse events (AEs) in single-dose study

  The incidence of adverse reactions

  All adverse events are collected from the signing of written informed consent up to 24 hours after drug administration.

• Adverse events (AEs) in multiple-dose study

  The incidence of adverse reactions

  All adverse events are collected from the signing of written informed consent up to 72 hours after the last drug administration.

• Serious adverse events (SAEs) in single-dose study

  All serious adverse events that occur during the clinical study

  All serious adverse events are collected from the signing of written informed consent up to 24 hours after drug administration.

• Serious adverse events (SAEs) in multiple-dose study

  All serious adverse events that occur during the clinical study

  All serious adverse events are collected from the signing of written informed consent up to 72 hours after the last drug administration.

Secondary Outcomes (4)

• 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

• 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 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 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)

Study Arms (2)

Test group

EXPERIMENTAL

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

Placebo group

PLACEBO COMPARATOR

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

Interventions

Felbinac trometamol eye drop DRUG

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.

Test group

Placebo eye drop DRUG

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.

Placebo group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tongren Hospital: lead

Study Sites (1)

Beijing Tongren Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Study Officials

• Xiuli Zhao, Ph.D.

  Beijing Tongren Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Wu, Ph.D.

CONTACT

010-58268422; trdrug@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is designed as single dose escalation in the healthy subjects，the subjects are 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 is designed as multiple dose escalation in the healthy subjects，the subjects are 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 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.

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 20, 2021
• Study Start: October 21, 2020
• Primary Completion: October 31, 2021
• Study Completion: December 31, 2021
• Last Updated: October 20, 2021

Record last verified: 2021-09

Locations

CN (1)