AR-12286 in Combination With Latanoprost

Study Overview
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Brief Summary
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This is a double-masked, randomized, multi-center, active-controlled, crossover comparison of the addition of AR-12286 or timolol to latanoprost in the treatment of elevated intraocular pressure (IOP).

Official Title
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A Phase 2, Double-masked, Randomized, Active-controlled, Crossover Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-12286 or Timolol Added to Patients With Elevated Intraocular Pressure Currently Using Latanoprost

Conditions
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Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: Latanoprost 0.005%
* Drug: AR-12286 Ophthalmic Solution 0.5%
* Drug: Timolol maleate ophthalmic solution 0.5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or greater. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). Currently using prostaglandin analogue (monotherapy or combination therapy) O.U. ≥ 1 month at time of study entry (first qualification visit) in study eye(s). Qualification Visit 1 (Screening) IOP at 16:00 hrs: PG monotherapy patients: ≥ 18 mm Hg; Combination therapy patients: >= 16 mm Hg. Qualification Visit 2 (post latanoprost run-in) IOP ≥ 20 mm Hg at 08:00 hrs and 10:00 hrs, IOP ≥ 18 mm Hg at 16:00 hrs in study eye(s). (Note: combination therapy may include any combination of topical ocular hypotensive agents). 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: In either eye: Previously randomized to treatment in a clinical study of AR-12286. Intraocular pressure > 36 mm Hg. History of acute angle-closure glaucoma, or closed or narrow angle upon gonioscopy Known hypersensitivity or contraindication to timolol maleate ophthalmic solution, or any component of the formulation (benzalkonium chloride, etc.), or to topical anesthetics, including history of conjunctival hyperemia with topical latanoprost of severity greater than 1 on a 0-3 scale. Ocular trauma within the past six months, or ocular surgery or laser treatment within the past three months. Contact lens wear within 30 minutes of instillation of study medication. PG monotherapy patients: Ocular hypotensive medication (other than prostaglandin) within 4 weeks of Visit 0 (Study entry, first qualification visit). Combination therapy patients: Ocular hypotensive medication (other than prostaglandin and current additional agent) within 4 weeks of Visit 0 (Study entry, first qualification visit). Conjunctival hyperemia of grade 2+ or greater at Visit 1. Any other ocular medication within 4 weeks of Visit 1 with the exception of 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 treatment with only latanoprost for two periods of up to 4 weeks is not judged safe (e.g., advanced glaucomatous optic nerve head or visual field loss). Any abnormality preventing reliable applanation tonometry of either eye. In study eye(s): Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle closure. Note: Previous laser peripheral iridotomy is acceptable. Previous glaucoma intraocular surgery or laser procedures. Refractive surgery (e.g., radial keratotomy, PRK, LASIK, etc.). Central corneal thickness greater than 600 µ. Systemic: Known bronchial asthma (history or current), severe chronic obstructive pulmonary disease, sinus bradycardia, second or third degree atrioventricular block or overt cardiac failure. 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 that could have a substantial effect on IOP 4 weeks prior to screening, or anticipated during the study. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AR-12286<br>AR-12286 Ophthalmic Solution 0.5% | Drug: Latanoprost 0.005%<br>* q.d.<br>* Other names: Xalatan(R);Drug: AR-12286 Ophthalmic Solution 0.5%<br> <br> |
| Active Comparator: Timolol<br>Timolol maleate ophthalmic solution 0.5% | Drug: Latanoprost 0.005%<br>* q.d.<br>* Other names: Xalatan(R);Drug: Timolol maleate ophthalmic solution 0.5%<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular pressure | The primary efficacy endpoint will be the mean IOP across subjects within treatment group at each study visit at each post-treatment timepoint. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular safety | Safety endpoints will be visual acuity, objective biomicroscopic and ophthalmoscopic examination, and subjective comfort as measured by adverse events in response to subject symptom queries. | 28 days | 
| Systemic safety | Heart rate, and blood pressure. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glaucoma, Intraocular pressure, Ocular hypertension