Study Comparing the Safety and Efficacy of AR-13324 to Latanoprost in Patients With Elevated Intraocular Pressure

Study Overview
=================
Brief Summary
-----------------
Double-masked, randomized, multi-center, dose-response, active-controlled parallel-comparison of AR-13324 to latanoprost

Official Title
-----------------
A Phase 2, Double-masked, Randomized, Multi-center, Active-controlled, Dose-response Parallel-group Study Comparing the Safety and Ocular Hypotensive Efficacy of AR-13324 to Latanoprost in Patients With Elevated Intraocular Pressure

Conditions
-----------------
Ocular Hypertension, Open Angle Glaucoma

Intervention / Treatment
-----------------
* Drug: AR-13324 Ophthalmic Solution 0.01%
* Drug: AR-13324 Ophthalmic Solution 0.02%
* Drug: Latanoprost ophthalmic solution 0.005%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or greater. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). Unmedicated (post-washout) Intraocular Pressure (IOP) ≥ 24 mm Hg at 2 eligibility visits (08:00 hr), 2-7 days a part, and ≥ 22 mm Hg at 10:00 and 16:00 hrs at the second qualification visit. If only one eye meets the IOP criteria it must be the same eye that met the criteria at all the qualification timepoints. Corrected visual acuity in each eye +1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200). Able and willing to give signed informed consent and follow study instructions. Exclusion Criteria: Ophthalmic Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle closure or narrow angles. Note: Previous laser peripheral iridotomy is NOT acceptable. IOP > 36 mm Hg. Known hypersensitivity to any component of the formulation (benzalkonium chloride, etc.), or to topical anesthetics. Previous glaucoma intraocular surgery or glaucoma laser procedures in study eye(s, e.g., laser trabeculoplasty). Refractive surgery in study eye(s) (e.g., radial keratotomy, photorefractive keratectomy (PRK), laser eye surgery (LASIK), etc.). Ocular trauma within the past six months, or ocular surgery or laser treatment within the past three months prior to screening. Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at screening (Visit 0), or a history of herpes simplex keratitis Ocular medication of any kind within 30 days of Visit 0, with the exception of a) ocular hypotensive medications (which must be washed out according to the provided schedule), b) lid scrubs (which may be used prior to, but not after Visit 0) or c) lubricating drops for dry eye (which may be used throughout the study). Clinically significant ocular disease (e.g. uveitis, severe keratoconjunctivitis sicca) which might interfere with the study, including glaucomatous damage so severe that washout of ocular hypotensive medications for one month is not judged safe (i.e., cup-disc ratio > 0.8). Central corneal thickness greater than 600 µm. Any abnormality preventing reliable applanation tonometry of either eye. Systemic: Clinically significant abnormalities (as determined by the treating physician) in laboratory tests at screening. Known hypersensitivity or contraindication to latanoprost. Clinically significant systemic disease (e.g., myasthenia gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere with the study. Participation in any investigational study within 30 days prior to screening. Changes of systemic medication that could have a substantial effect on IOP within 30 days prior to screening, or anticipated during the study. Due to the current status of the preclinical safety program, women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. An adult woman is considered to be of childbearing potential unless she is one year post-menopausal or three months post-surgical sterilization. All females of childbearing potential must have a negative urine pregnancy test result at the screening examination and must not intend to become pregnant during the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AR-13324 Ophthalmic Solution 0.01%<br>1 drop to study eye once daily | Drug: AR-13324 Ophthalmic Solution 0.01%<br>* Administered to study eye, once daily (QD) in the evening (PM) for 28 days<br>|
| Experimental: AR-13324 Ophthalmic Solution 0.02%<br>1 drop to study eye once daily | Drug: AR-13324 Ophthalmic Solution 0.02%<br>* Administered to study eye, QD in the PM for 28 days<br>* Other names: Netarsudil;|
| Active Comparator: Latanoprost Ophthalmic Solution 0.005%<br>1 drop to study eye once daily | Drug: Latanoprost ophthalmic solution 0.005%<br>* Administered to study eye, QD in the PM for 28 days<br>* Other names: Latanoprost;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular Pressure (IOP) | The primary efficacy endpoint was the mean IOP across subjects within treatment group on each day at each post-treatment timepoint. IOP was measured at 0800, 1000, and 1600 hours on days 0, 14, and 28. IOP was also measured at 0800 hours on Day 7 and follow-up days 29 and 30. | Study treatment was administered for 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of Exposure | Exposure to study medication in days for all treatment groups. | 28 Days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glaucoma