Study Comparing the Safety and Efficacy of BOL-303259-X to Latanoprost in Subjects With Glaucoma or Ocular Hypertension

Study Overview
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Brief Summary
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The objective of this clinical investigation is to determine the most effective drug concentration(s) of BOL-303259-X in the reduction of IOP in order to support further clinical development of an appropriate dose with regard to efficacy, and ocular and systemic safety.

Official Title
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A Randomized, Multicenter, Single-Masked, Parallel-Group Dose Finding Study Comparing the Safety and Efficacy of BOL-303259-X to Latanoprost in Subjects With Open Angle Glaucoma or Ocular Hypertension

Conditions
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Intraocular Pressure

Intervention / Treatment
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* Drug: BOL-303259-X
* Drug: Latanoprost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a diagnosis of open angle glaucoma (OAG) or ocular hypertension (OH) in one or both eyes. IOP requirements at Visit 3, A mean/median IOP ≥ 26 mmHg at a minimum of 1 time point, ≥ 24 mmHg at a minimum of 1 time point, and ≥ 22 mmHg at 1 time point in the same eye, and Mean/median IOP ≤ 32 mmHg in both eyes at all 3 measurement time points. Subjects with best-corrected visual acuity (BCVA), using Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, of +0.7 logMAR units (Snellen equivalent  20/100) or better in either eye. Exclusion Criteria: Subjects with a known hypersensitivity or contraindications to latanoprost or any of the ingredients in the study drugs. Subjects with known contraindications to nitric oxide (NO) treatment. Subjects whose central corneal thickness was greater than 600um in either eye. Subjects with any condition that prevented reliable applanation tonometry in either eye. Subjects with advanced glaucoma and subjects with a cup/disc ratio greater than 0.8 or a history of split fixation, or a field loss threatening fixation in either eye. Subjects with previous or active corneal disease. Subjects with a history of severe dry eye. Subjects with monophthalmia. Subjects with optic disc hemorrhage. Subjects with a history of central retinal vein and artery occlusion. Subjects with a history of macular edema. Subjects with any intraocular infection, inflammation, or laser surgery within the previous 6 months from Visit 1 (Screening). Subjects who had incisional ocular surgery or severe trauma within the previous 6 months from Visit 1 (Screening). Subjects with very narrow angles (3 quadrants with less than Grade 2 according to Shaffer's anterior chamber angle grading system) and subjects with angle closure, congenital and secondary glaucoma, and subjects with history of angle closure in either eye. Subjects with a diagnosis of a clinically significant or progressive retinal disease in either eye. Subjects who were expected to require treatment with ocular or systemic corticosteroids. Subjects who were in need of any other topical or systemic treatment of OAG or OHT. Subjects with an anticipated need to initiate or modify medication (systemic or topical) that was known to affect IOP during the study period.

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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOL-303259-X<br>ophthalmic solution | Drug: BOL-303259-X<br>* ophthalmic solution, various concentrations, once daily (QD) 28 days<br>* Other names: latanoprostene bunod;|
| Active Comparator: Latanoprost<br>ophthalmic solution | Drug: Latanoprost<br>* 0.005% ophthalmic solution, QD 28 days<br>* Other names: Xalatan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Diurnal IOP at Visit 6 (Day 28) | Determine the most effective drug concentration(s) of BOL-303259-X in the reduction of intraocular pressure (IOP) and compared to latanoprost | Baseline and Visit 6 (Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Diurnal IOP at Visits 4,5, and 7 | Determine the most effective drug concentration(s) of BOL-303259-X in the reduction of intraocular pressure (IOP) and compared to latanoprost | Baseline and Visit 4 (Day 7), Visit 5 (day 14), and Visit 7 (Day 29) | 
| IOP </=18mm Hg | Determine the number of subjects with mean diurnal IOP </=18 mm Hg with BOL-303259-X versus latanoprost ophthalmic solution | Visit 4 (Day 7), Visit 5 (day 14), Visit 6 (Day 28) and Visit 7 (Day 29) | 
| Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28) | The change in the observed mean study eye IOP from baseline (Visit 3, Day 1) at specified time points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28) | baseline and Visit 6 (Day 28) | 
| Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) | The change in the observed mean study eye IOP from baseline (Visit 3, Day 1) at specified time points (points 8 AM, 12 PM, and 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) | baseline and Visits 4, 5 and 7 (Days 7, 14, and 29) |