A Clinical Trial to Evaluate Tolerability and Pharmacokinetics of HL217 Eye Drop in Healthy Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability and PK parameters in healthy subjects.

Detailed Description
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The purpose of this study is to evaluate the safety, tolerability and PK parameters of HL217 after single eye drop administration at different doses in healthy subjects.

Official Title
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A Dose Block-randomized, Double-blind, Placebo Controlled, Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics After Single Dosing of HL217 Eye Drop in Healthy Male Subjects

Conditions
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Healthy Subject

Intervention / Treatment
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* Drug: Cohort 1: HL217 Ophathalmic Solution QD
* Drug: Cohort 2: HL217 Ophathalmic Solution BID
* Drug: Cohort 3: HL217 Ophthalmic Solution QID
* Drug: Placebo Ophthalmic solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subject, aged between 18 and 50 years inclusive Non-smoker subject or smoker of not more than 10 cigarettes a day and able to stop smoking 24 hour prior to admission until discharge Body weight ≥ 50 kg and BMI between 18 and 30 kg/m² Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination) including complete ocular examination Normal Blood Pressure (BP) and Heart Rate (HR) after 10 minutes in supine position: 90 mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg 45 mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg 40 bpm ≤ HR ≤ 100 bpm Or considered NCS by investigators Normal ECG recording on a 12-lead ECG: 120 < PR < 200 ms QRS < 120 ms QTcf ≤ 430 ms No sign of any trouble of sinusal automatism Or considered NCS by investigators Laboratory parameters within the normal range of the laboratory (haematological, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator Normal dietary habits Signing a written informed consent prior to selection Exclusion Criteria: Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic, infectious or ocular disease Frequent headaches and / or migraine, recurrent nausea and / or vomiting Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP or DBP equal to or greater than 20 mmHg within two minutes when changing from the supine to the standing position Blood donation (including in the frame of a clinical trial) within 2 months before administration or apheresis within 20 days before administration General anaesthesia within 3 months before administration Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician (including allergy to fluorescein) Inability to abstain from intensive muscular effort No next of kin, easily accessible, in case of emergency Any drug or herbal medicine intake (except paracetamol) during the last 14 days prior to the first administration, any over the counter medicine or vitamin during the last 7 days prior to the first administration Subjects who have taken drug metabolizing enzyme inducing agents and inhibitors such as barbitals within a month prior to the first administration History or presence of drug or alcohol abuse (alcohol consumption > >21 units per week) Excessive consumption of beverages with xanthine bases (> 5 cups or glasses / day) and not able to stop 24h prior to admission until discharge Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 Major surgery (general or ocular) within 28 days prior to randomization or major surgery planned during the next 6 months Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development Subjects within an exclusion period of a previous study or subjects who have taken any investigational product from other clinical trials within 60 days from the start of the study (from the administration of investigational product) Subjects with previous participation in the current study Subject under administrative or legal supervision Subjects with an allergy to Fluorescein History of any ocular surgery within the past 6 months prior to study participation Subject who have intraocular pressure > 21 mmHg Subject with acute or chronic eye problems that require eye drop at the time of screening Best-corrected ETDRS visual acuity score ≤ 85 (Snellen equivalent 20/20) Subject who need to wear contact lens during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: HL217 Ophathalmic Solution QD<br>HL217 3mg/mL, Ophthalmic solution, two drop once a day | Drug: Cohort 1: HL217 Ophathalmic Solution QD<br>* Cohort 1 (Once a day)<br>* Other names: 3mg/mL;|
| Experimental: Cohort 2: HL217 Ophathalmic Solution BID<br>HL217 3mg/mL, Ophthalmic solution, two drop twice a day | Drug: Cohort 2: HL217 Ophathalmic Solution BID<br>* Cohort 2 (Twice a day)<br>* Other names: 3mg/mL;|
| Experimental: Cohort 3: HL217 Ophthalmic Solution QID<br>HL217 3mg/mL, Ophthalmic solution, two drop four times a day | Drug: Cohort 3: HL217 Ophthalmic Solution QID<br>* Cohort 3 (Four times a day)<br>* Other names: 3mg/mL;|
| Placebo Comparator: Placebo Ophthalmic solution<br>Placebo Ophthalmic solution, two drop once or twice or four times a day | Drug: Placebo Ophthalmic solution<br>* Placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical parameter: Adverse Events (AE) | AEs will be coded according to the MedDRA. They will be classified into pre-defined standard categories according to chronological criteria | During 72hours | 
| Local tolerance: Redness, Tingling and Other ophthalmic adverse events | Redness, tingling and others should be checked | During 72hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessment: Cmax | observed maximum plasma concentration of HL217 | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: Tmax | first time to reach Cmax | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: AUClast | area under the plasma concentration curve from administration up to the last quantifiable concentration at time 72h | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: AUCinf | area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: Kel | elimination rate constant | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: T1/2 | plasma elimination half-life | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: %AUCextra | percentage of extrapolated AUCinf | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: Cl/F | clearance | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour | 
| Pharmacokinetic assessment: Vd/F | volume of distribution | 0hour (Pre-dose), 0.25hour, 0.5hour, 0.75hour, 1hour, 2hour, 3hour, 4hour, 6hour, 8hour, 11hour, 12hour, 24hour, 72hour |