Study of AR-13324 in Patients With Elevated Intraocular Pressure

Study Overview
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Brief Summary
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In this double-masked, vehicle-controlled, dose-response study, subjects will be randomized to receive AR-13324 Ophthalmic Solution 0.01%, 0.02%, and 0.04% or its vehicle (one eye), once daily (QD)in the morning (AM) for 7 days. The first dose and last dose will be administered in the clinic. Ocular safety and ocular hypotensive efficacy will be evaluated in the clinic throughout the study.

Official Title
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A Phase 2, Double-masked, Randomized, Placebo-controlled, Dose-response Study Assessing the Safety and Ocular Hypotensive Efficacy of Three Doses of AR-13324 Ophthalmic Solution in Patients With Elevated Intraocular Pressure

Conditions
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Ocular Hypertension, Open Angle Glaucoma

Intervention / Treatment
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* Drug: AR-13324 Ophthalmic Solution 0.01%
* Drug: AR-13324 Ophthalmic Solution 0.02%
* Drug: AR-13324 Ophthalmic Solution 0.04%
* Other: AR-13324 Ophthalmic Solution Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or greater. 18 years of age or greater. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). Unmedicated (post-washout, p.r.n.) IOP ≥ 24 mm Hg in one or both eyes at 08:00 hours, ≥ 21 mm Hg at 10:00, 12:00 and 16:00 hours on post-washout measurement (Visit 1). 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: Either eye Intraocular pressure > 36 mm Hg Known hypersensitivity to any component of the formulation or to topical anesthetics, (benzalkonium chloride, etc.) Ocular trauma within the past six months, or ocular surgery or laser treatment within the past three months. Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at baseline (Visit 1), or history of herpes simplex keratitis. Contact lens wear within 30 minutes of instillation of study medication. Ocular medication of any kind within 30 days of Visit 2, 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 2) or c) lubricating drops for dry eye (which may be used throughout the study), Clinically significant ocular disease (e.g. corneal edema, 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 (e.g., advanced glaucomatous optic nerve head or visual field loss). Any abnormality preventing reliable applanation tonometry in either eye. Study eye: Glaucoma: pseudoexfoliation or pigment dispersion component, history of acute angle-closure glaucoma, or closed or narrow angle upon gonioscopy. Note: Previous laser peripheral iridotomy is NOT acceptable. Previous glaucoma intraocular surgery or laser procedures such as argon laser trabeculoplasty (ALT), selective laser trabeculoplasty (SLT) or micropulse laser trabeculoplasty ( MLT), as well as refractive procedures such as radio keratotomy (RK), laser eye surgery (LASIK), photorefractive keratectomy (PRK), or collagen cross linking. Central corneal thickness greater than 600 μm. General/Systemic: Clinically significant abnormalities in laboratory tests at screening, recognizing that subjects are not fasting at the time of drawing blood. Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, hepatic, renal, cardiovascular or endocrine disorders) which might interfere with the study. Participation in any investigational study within the past 30 days. Changes of systemic medication during the study that could have a substantial effect on IOP within 30 days prior to screening, or anticipated during the study. Due to status of 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
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Minimum Age: 18 Years
Maximum Age: 99 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: 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 morning (AM) for 7 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 AM for 7 days<br>* Other names: Netarsudil;|
| Experimental: AR-13324 Ophthalmic Solution 0.04%<br>1 drop to study eye once daily | Drug: AR-13324 Ophthalmic Solution 0.04%<br>* Administered to study eye, QD AM for 7 days<br>|
| Placebo Comparator: AR-13324 Ophthalmic Solution Vehicle<br>1 drop to study eye once daily | Other: AR-13324 Ophthalmic Solution Vehicle<br>* Administered to study eye, QD AM for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular Pressure (IOP) | The primary efficacy outcome was the mean IOP across subjects within treatment group at each post-treatment timepoint of Day 8. Instillation of study treatment commenced on Day 2 following measurement of IOP. IOP was measured at 0800, 1000, 1200 and 1600 hours on days 2 and 8. IOP was also measured at 0800 hours on Day 4. | Study treatment was administered for 7 days; starting on Day 2 and ending on Day 8. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intraocular pressure, visual field, Ocular hypertension or open angle glaucoma