Comparing Safety and Efficacy of BOL-303259-X With Timolol Maleate in Subjects With Open-Angle Glaucoma or Ocular Hypertension

Study Overview
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Brief Summary
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In participants with a diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT), the primary objective is to demonstrate that the mean IOP reduction after 3 months of treatment with BOL-303259-X once daily (QD) is non-inferior to timolol maleate 0.5% twice daily (BID). The secondary objective is to demonstrate the superiority of BOL-303259-X QD to timolol maleate 0.5% BID. This assessment will be performed if the non-inferiority of BOL-303259-X QD to timolol maleate 0.5% BID is determined. An open label safety phase will be conducted at the end of Visit 6 (3 months) where all participants will receive BOL-303259-X QD for an additional 9 months.

Official Title
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A Randomized, Multicenter, Double-Masked, Parallel-Group Study Comparing the Safety and Efficacy of BOL-303259-X Ophthalmic Solution With Timolol Maleate Ophthalmic Solution 0.5% in Subjects With Open-Angle Glaucoma or Ocular Hypertension.

Conditions
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Open-Angle Glaucoma, Ocular Hypertension

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a diagnosis of OAG (including pigmentary or pseudoexfoliative) or OHT in 1 or both eyes. Participants must meet the following IOP requirements at Visit 3 mean/median IOP ≥ 24 mmHg at a minimum of 2 time points in the same eye IOP ≤ 36 mmHg at all 3 measurement time points in both eyes. Participants with a best-corrected visual acuity (BCVA), using the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, of +0.7 logMAR units (Snellen equivalent of approximately 20/100) or better in either eye. Exclusion Criteria: Participants with known hypersensitivity or contraindications to latanoprost, NO treatment, timolol maleate, other beta-adrenergic receptor antagonists or any of the ingredients in the study drugs. Participants with a central corneal thickness greater than 600 μm in either eye. Participants with advanced glaucoma and participants with a cup/disc ratio greater than 0.8 or a history of split fixation, or a field loss threatening fixation in either eye. Participants who do not have an intact posterior capsule in either eye . Participants with aphakia in either eye. Participants with previous or active corneal disease in either eye. Participants with current or a history of severe dry eye in either eye. Participants with current or a history of optic disc hemorrhage in either eye. Participants with current or a history of central/branch retinal vein or artery occlusion in either eye. Participants with current or a history of macular edema in either eye. Participants with very narrow angles (3 quadrants with less than Grade 2 according to Shaffer's anterior chamber angle grading system) and Participants with angle closure,congenital, and secondary glaucoma, and participants with history of angle closure in either eye. Participants with a diagnosis of a clinically significant or progressive retinal disease in either eye. Participants with any intraocular infection or inflammation in either eye within 3 months(90 days) prior to Visit 1 (Screening). Participants with a history of ocular laser surgery in either eye within the 3 months(90 days) prior to Visit 1 (Screening). Participants with a history of incisional ocular surgery or severe trauma in either eye within 3 months (90 days) prior to Visit 1 (Screening).

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOL-303259-X<br>BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye(s). | Drug: BOL-303259-X<br>* Topical ocular BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning for 3 months (visit 6).<br>Drug: BOL-303259-X<br>* All participants will receive topical ocular BOL-303259-X QD in the evening for an additional 9 months from Visit 6 through Visit 9 (1 year)<br>|
| Active Comparator: Timolol<br>Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye(s). | Drug: Timolol<br>* Timolol will be administered BID once in the morning and once in the evening for 3 months (Visit 6)<br>Drug: BOL-303259-X<br>* All participants will receive topical ocular BOL-303259-X QD in the evening for an additional 9 months from Visit 6 through Visit 9 (1 year)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean IOP | Mean intraocular pressure (IOP) in study eye measured at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3). | 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate - IOP ≤ 18 mm Hg | Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months | 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3). | 
| Response Rate - IOP Reduction ≥ 25% | Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months | 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intraocular pressure