A Safety, Tolerability and Pharmacokinetics Study of R932348 Eye Drops in Patients With Dry Eye Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety, tolerability and pharmacokinetics of R348 eye drops in patients with dry eye disease.

Detailed Description
-----------------
This is a randomized, double-blind, placebo-controlled single and multiple ascending dose study to evaluate the ocular tolerability, safety, and pharmacokinetics of R348 administered in patients with mild to moderate keratoconjunctivitis sicca (KCS).

Official Title
-----------------
A Phase 1, Single Center, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose, Pharmacokinetics, Tolerability and Safety Study of R932348 Ophthalmic Solution in Patients With Mild to Moderate Keratoconjunctivitis Sicca

Conditions
-----------------
Keratoconjunctivitis Sicca

Intervention / Treatment
-----------------
* Drug: R348 Ophthalmic Solution, 0.2%
* Drug: R348 Ophthalmic Solution, 0.5%
* Drug: R348 Ophthalmic Solution, 1.0%
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Mild to moderate Keratoconjunctivitis Sicca. A corrected visual acuity in both eyes of 20/40 or better. An intraocular pressure of < 21 mm Hg with a difference between eyes of < 6 mm Hg. Exclusion Criteria: History or evidence of ocular infection, inflammation, or conjunctivitis within 2 months prior to the first dosing day. History or evidence of blepharitis requiring the use of antibiotics or eye scrubs within 2 months prior to the first dosing day. History of herpes simplex keratitis at any time. Current ocular allergy symptoms. Recent use of eye medications such as steroids or cyclosporine Refractive eye surgery within 12 months of the first dosing day. Other eye surgeries within 4 months of the first dosing day. Current use of contact lenses or discontinuation of contact lens use within 2 weeks of the first dosing day. Receipt of any blood or blood products within 90 days prior to the first dosing day. Participation in any clinical study within 30 days prior to the first dosing day. History of disease, or currently have a significant illness or abnormal laboratory finding as determined by your study doctor. Positive for hepatitis B, hepatitis C or HIV. Smoked regularly within 12 months of first dosing day. History of substance abuse, drug addiction or alcoholism.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: R348 Ophthalmic Solution, 0.2%<br>R348 Ophthalmic Solution, 0.2%, single (1 day) and multiple ascending dose (13 days) followed by a single dose on the fourteenth day. | Drug: R348 Ophthalmic Solution, 0.2%<br>* R348 Ophthalmic Solution, 0.2% single and multiple ascending dose<br>* Other names: R932348;Drug: Placebo<br>* Placebo, single and multiple ascending dose<br>|
| Active Comparator: R348 Ophthalmic Solution, 0.5%<br>R348 Ophthalmic Solution, 0.5%, single (1 day) and multiple ascending dose (13 days) followed by a single dose on the fourteenth day. | Drug: R348 Ophthalmic Solution, 0.5%<br>* R348 Ophthalmic Solution, 0.5%, single and multiple ascending dose<br>* Other names: R932348;Drug: Placebo<br>* Placebo, single and multiple ascending dose<br>|
| Active Comparator: R348 Ophthalmic Solution, 1.0%<br>R348 Ophthalmic Solution, 1.0%, single (1 day) and multiple ascending dose (13 days) followed by a single dose on the fourteenth day. | Drug: R348 Ophthalmic Solution, 1.0%<br>* R348 Ophthalmic Solution, 1.0%, single and multiple ascending dose<br>* Other names: R932348;Drug: Placebo<br>* Placebo, single and multiple ascending dose<br>|
| Placebo Comparator: Placebo<br>Placebo, single (1 day) or multiple ascending dose (13 days) followed by a single dose on the fourteenth day. | Drug: Placebo<br>* Placebo, single and multiple ascending dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in corneal fluorescein staining |  | Baseline and Visits 4, 8 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in conjunctival lissamine green staining |  | Baseline and Visits 4, 8 and 12 |