A Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of GLH8NDE After Single and Mutiple Ocular Administrations in Healthy Korean and Caucasian Volunteers

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled phase 1 clinical trial to evaluate the safety, tolerability and pharmacokinetic characteristics of GLH8NDE after single and multiple ocular administrations in healthy Korean and Caucasian volunteers

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 1 Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of GLH8NDE After Single and Mutiple Ocular Administrations in Healthy Korean and Caucasian Volunteers

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: 5% GLH8NDE
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subject who, at the time of screening, are the age between 20 and 50 years Subject who has body weight between 55.0 and 90.0 kg, and BMI between 18.0 and 27.0 Subject who signed and dated the informed consent form after understanding fully to hear a detailed explanation in the clinical trial Exclusion Criteria: A subject who has a evidence or history of clinically significant hepatic, renal, neurologic, pulmonary, endocrine, urological, psychiatric, cardiovascular, hematological, oncological, etc. A subject who has a history of disease with myocardial infarction, stroke, arrhythmia, hypotension (90 mmHg amine or diastolic blood pressure less than 50 mmHg at screening), uncontrolled hypertension (greater than 170 mmHg diastolic blood pressure or 100 mmHg diastolic blood pressure at screening), coronary artery, or who has a current abnormality A subject with a history of hypersensitivity to the drug (aspirin, antibiotics, etc.) or clinical significant hypersensitivity reactions A subject with the following findings in paperweight, visual acuity test, front eye photo, corneal refraction test, intraocular pressure test, slit lamp microscopy examination, fundus examination, tear break-up time examination, tear secretion test, OSDI (ocular surface disease index) are excluded A subject with suspected history or symptoms of visual organs, including keratitis, uveitis, retinitis, dry eye and strabismus A subject who has had eye surgery (including those who have received more than 6 months for eye laser surgery) A subject at least one eye with an intra-ocular pressure of 22 mmHg or more at the screening At the screening, tear break-up time of at least one eye in both eyes is less than 10 seconds and diagnosed as dry eye according to OSDI test A subject whose ratio for at least one eye in both eyes during screening is less than 10 mm as measured for 5 minutes in an Un-anesthetized Schirmer's test There are side effects to people who wear contact lenses after wearing them or within a month A subject with a history of drug abuse or a positive urine drug screening for drug abuse A subject who has participated in any other clinical trials and bioequivalence had medication within 6 months prior to the first administration of investigational product (The end date of another clinical trial is based on the last day of the administration) A subject who has taken any ethical-the-counter drug or herbal drug within 2 weeks has taken any over-the-counter drug or vitamin include artificial tears within 1 week before the investigational product A subject who has donated whole blood within 2 months or blood components within 1 month prior to the investigational product administration History of regular alcohol consumption exceeding 21 units/week (1 unit = 10 g of pure alcohol) within 60 days before the investigational product or non-stop the alcohol drinking The current smoker, but except the subject to quit the smoke over 90 days Recognized contraceptive methods (e.g. your and your partner's infertility surgery, your partner's intrauterine device (IUD), cervical caps or contraceptive diaphragms for use with spermicides) Single block), cervical cap or contraceptive diaphragm with male condom (double block)] A subject who have to work that cause excessive eye fatigue during this clinical trial A subject who is not eligible for the study due to reasons on the investigators' judgement

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The A group in 5% GLH8NDE<br>Three times administration both eyes, each 1 drop in Korean | Drug: 5% GLH8NDE<br>* 5% GLH8NDE as eye drops<br>|
| Placebo Comparator: The A group in placebo<br>Three times administration both eyes, each 1 drop in Korean | Drug: Placebos<br>* Placebo as eye drops<br>|
| Experimental: The B group in 5% GLH8NDE<br>Six administration both eyes, each 1 drop in Korean | Drug: 5% GLH8NDE<br>* 5% GLH8NDE as eye drops<br>|
| Placebo Comparator: The B group in placebo<br>Six administration both eyes, each 1 drop in Korean | Drug: Placebos<br>* Placebo as eye drops<br>|
| Experimental: The C group in 5% GLH8NDE<br>Six administration both eyes, each 2 drop in Korean | Drug: 5% GLH8NDE<br>* 5% GLH8NDE as eye drops<br>|
| Placebo Comparator: The C group in placebo<br>Six administration both eyes, each 2 drop in Korean | Drug: Placebos<br>* Placebo as eye drops<br>|
| Experimental: The D group in 5% GLH8NDE<br>Six administration both eyes, each 2 drop in Caucasian | Drug: 5% GLH8NDE<br>* 5% GLH8NDE as eye drops<br>|
| Placebo Comparator: The D group in placebo<br>Six administration both eyes, each 2 drop in Caucasian | Drug: Placebos<br>* Placebo as eye drops<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | To 18 days after first IP administration | Between 1 day before first IP administration and 18 days | 
| Vital signs in blood pressure | Whether out of normal range at Blood pressure (SBP, DBP) | Each point at Screening(between 2 day and 28 day before IP administration), 1, 2, 4, 6, 8, 10, 11 days, and post-study visit(between 16 and 18 days) | 
| Vital signs in pulse | Whether out of normal range at Pulse rate | Each point at Screening(between 2 day and 28 day before IP administration), 1, 2, 4, 6, 8, 10, 11 days, and post-study visit(between 16 and 18 days) | 
| Vital signs in temperature | Whether out of normal range in temperature at eardrum | Each point at Screening(between 2 day and 28 day before IP administration), 1, 2, 4, 6, 8, 10, 11 days, and post-study visit(between 16 and 18 days) | 
| Physical examinations in weight change | Weight change in kilograms | Change trend of the each point among screening(between 2 day and 28 day before IP administration), 1, 2, 4, 6, 8, 10, 11 days, and post-study visit(between 16 and 18 days) | 
| Clinical laboratories in blood sample | Whether abnormal blood chemistry | Each point at day 1, 2, 4, 6, 8, 10, and 11 | 
| Clinical laboratories in blood sample | Whether positive at Type B hepatitis, Type C hepatitis, HIV, and Syphilis | Each point at day 1, 2, 4, 6, 8, 10, and 11 | 
| 12-lead ECG in clinical significance | Whether out of normal range QRS complex | Each point at Screening(between 2 day and 28 day before IP administration), 1, 4, 11 days, and post-study visit(between 16 and 18 days) | 
| Ophthalmic symptom | To 18 days after first IP administration | Each point at Day 1, 2, 4, 6, 8, 10, and 11 | 
| Ophthalmic examination | Tear break-up time examination | Each point at Screening(between 2 day and 28 day before IP administration), 2, 11 days, and post-study visit(between 16 and 18 days) | 
| AUClast in ng·h/mL | One day administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| AUCinf in ng·h/mL | One day administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| Cmax in ng/mL | One day administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| Tmax in ng/mL | One day administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| t1/2 in hour | One day administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| AUCtau,ss in ng·h/mL | Mutiple dose administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| Cmax in ng/mL | Mutiple dose administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| Tmax in ng/mL | Mutiple dose administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| t1/2 in hour | Mutiple dose administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration | 
| R(Accumulation index) | Accumulation in dex at mutiple dose administration as GLH8NDE | Pre-dose, 10, 20, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours after last administration |