Clinical Study to Investigate the Efficacy and Safety of Orally Administered SA001 in Patients With Dry Eye Syndrome.

Study Overview
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Brief Summary
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This is a phase 2, multicenter, double-blind, placebo control, randomized study to evaluate the efficacy and safety of orally administered SA001 compared to placebo in patients with Dry Eye Syndrome. The clinical trial consists of a wash-out period of 14 days, a treatment period of 12 weeks, and a follow-up period of 1 week after administration of the Investigational Product. If the subject voluntarily signs the informed consent form(ICF), the investigator conducts screening tests and check medical history to evaluate the subject's suitability. As a result of the screening test, eligible subjects should stop using the prior medication for dry eye syndrome during the 14 days of observation period, and if necessary, subjects can use rescue drug(artificial tears) for the first 11 days, and then discontinue all eye drops including rescue drug(artificial tears) for 3 days. And all of these subjects will be randomized in a 1:1:1:1 ratio to receive 3 different doses of investigational product (SA001 or placebo) everyday for 12 weeks. During the treatment period, If necessary, subjects can use the rescue drug (artificial tears), and the number of administration of rescue drug is limited to 3 times a day, and when used, the administration time should be recorded in the subject's diary. Subjects should visit to the study site on 2, 4, 8 and 12 weeks after starting dosing investigational product. Efficacy evaluation results are collected from both eyes, and the primary evaluation variable is analyzed using the test results collected from 'Worse eye' (the eye with the worse keratoconjunctival staining result among both eyes). Worse eye will be determined at the baseline visit and, if the results of both eyes are the same, the test result of the left eye is used.

Official Title
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A Multicenter, Placebo Controlled, 4-group Parallel Randomized, Double Blind, Phase II Study to Evaluate the Efficacy and Safety of Orally Administered SA001 in Patients With Dry Eye Syndrome.

Conditions
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Dry Eye Syndrome

Intervention / Treatment
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* Drug: SA001 Low dose
* Drug: SA001 Mid dose
* Drug: SA001 High dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 19 Patient who meets all of the following criteria in at least one of both eyes Fluorescein corneal staining score ≥ 2 Schirmer test ≤ 10mm in 5 mins Tear break-up time ≤ 10 secs Patient who diagnosed with dry eye syndrome at the time of screening and who have dry eye symptoms (dryness, discomfort, foreign body sensation, pain, vision fluctuation, etc.) Patient who agrees not to use eye drops other than the rescue drugs provided during the clinical trial period Patient who can understand the clinical trial and voluntarily signs an informed consent Exclusion Criteria: Clinically significant ophthalmic diseases not caused by dry eye disease (corneal surface disease, abnormal corneal sensitivity, abnormal tear excess, etc.) that may confuse the interpretation of clinical trial results In case of being treated with anti-inflammatory therapy for dry eye, such as steroid or non-steroidal anti-inflammatory eye drops, autologous serum eye drops, etc. In case of administration of steroids or immunosuppressants (azathioprine, tacrolimus, cyclosporine, mofetil mycophenolate, etc.) Patient who has worn contact lenses within 72 hours prior to screening or need to wear contact lenses during the clinical trial period A history of intraocular surgery within 90 days prior to screening Active eye infection symptoms such as anterior uveitis, anterior blepharitis, and Steven-Johnson syndrome Patient with an eye allergy or who are currently receiving treatment for an allergic eye disease (using antihistamines, etc.) Autoimmune disease (ex. Sjögren's syndrome, Rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, etc.) Patient who needs surgery due to surface elevation caused by Meibomian Gland Dysfunction (MGD) A history of corneal transplantation or neurotrophic keratitis Patient who has an intraocular pressure of 25 mmHg or higher in one or more of both eyes or have been diagnosed with glaucoma Patient who has undergone vision correction surgery such as LASIK (Laser-Assisted in Situ Keratomileusis) within 12 months prior to screening Patient who has undergone silicone lacrimal punctal occlusion or cauterization of the punctum within 90 days prior to screening. However, patient who has undergone collagen lacrimal punctal occlusion can be enrolled. Hypersensitivity to the ingredients of the investigational product including rebamipide Clinically significant liver, kidney, nervous system, immune system, respiratory or endocrine disease, blood/tumor disease, cardiovascular disease, mental disease (mood disorder, obsessive-compulsive disorder, etc.) or a history of those diseases Patient who shows the following examination findings at visit 1 (screening visit) WBC ≤ 4,000/mm3 Platelets ≤ 100,000/mm3 AST/ALT/ALP ≥ 3 times the upper limit of normal(ULN) Total bilirubin ≥ 1.5 times the upper limit of normal(ULN) A woman who has a positive Serum hCG test at the screening visit (Visit 1), or who does not agree to use at least one effective contraceptive method that is medically acceptable Take oral contraceptives during the study period Pregnant or lactating women A history of drug or alcohol abuse Participation in an investigational drug or device trial within 30 days prior to screening Any condition that, in the opinion of the investigator, would inappropriate to participate in the clinical trial

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>SA001 Low dose | Drug: SA001 Low dose<br>* 3 tablets b.i.d for 12 weeks<br>|
| Experimental: Group 2<br>SA001 Mid dose | Drug: SA001 Mid dose<br>* 3 tablets b.i.d for 12 weeks<br>|
| Experimental: Group 3<br>SA001 High dose | Drug: SA001 High dose<br>* 3 tablets b.i.d for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 3 tablets b.i.d for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fluorescein Corneal Staining(FCS) score from baseline to Day 84 |  | Baseline(Day0) and Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fluorescein Corneal Staining(FCS) score from baseline to Day 14, Day 28 and Day 56 |  | Baseline(Day0), Day 14, Day 28 and Day 56 | 
| Change in Lissamine Green Conjunctival Staining(LGCS) score from baseline to Day 14, Day 28, Day 56 and Day 84 |  | Baseline(Day0), Day 14, Day 28, Day 56 and Day 84 | 
| Change in Schirmer Test score from baseline to Day 14, Day 28, Day 56 and Day 84 |  | Baseline(Day0), Day 14, Day 28, Day 56 and Day 84 | 
| Change in Tear Break-Up Time(TBUT) from baseline to Day 14, Day 28, Day 56 and Day 84 |  | Baseline(Day0), Day 14, Day 28, Day 56 and Day 84 | 
| Change in Standard Patient Evaluation of Eye Dryness questionnaire(SPEED) from baseline to Day 14, Day 28, Day 56 and Day 84 |  | Baseline(Day0), Day 14, Day 28, Day 56 and Day 84 | 
| Total number of artificial tears use during the 12 weeks of treatment period |  | Day 84 |