BOL-303259-X With Timolol 0.5% in Subjects With Open-Angle Glaucoma or Ocular Hypertension

Study Overview
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Brief Summary
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This clinical investigation is being performed to compare the effect of BOL-303259-X dosed once daily (QD) with timolol maleate 0.5% dosed twice daily (BID) in reducing intraocular pressure (IOP) measured over a 24-hour period in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Official Title
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A Randomized, Single-Center, Open-Label, Crossover Study Comparing the 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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Ocular Hypertension, Open Angle Glaucoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a diagnosis of OAG or OHT in 1 or both eyes. Subjects who are treatment-naïve must meet the following IOP requirements at Visit 1 (Screening), and pretreated subjects must meet the following IOP requirements at Visit 2 (Washout): Intraocular pressure ≥ 22 mmHg in at least 1 eye and ≤ 36 mmHg in both eyes. Exclusion Criteria: Subjects who have been exposed to BOL-303259-X within 3 months prior to Visit 1 (Screening). Subjects with a history or presence of chronic generalized systemic disease that the Investigator feels might increase the risk to the subject or confound the results of the study. Subjects with an irregular daily sleep schedule. Subjects who are unable to wear sleep monitoring device for 7 days prior to laboratory study. Subjects with an anticipated need to initiate or modify medication (systemic or topical) that is known to affect IOP. Subjects for whom concomitant use of medications may interact with the safety or efficacy of a nitric oxide. Subjects with known hypersensitivity or contraindications to latanoprost or any of the ingredients in the study drugs. Subjects who are expected to require treatment with ocular or systemic corticosteroids. Subjects who are in need of any other topical or systemic treatment of OAG or OHT. Subjects who are unable to discontinue contact lens use during and for 24 hours before the laboratory study. Subjects with a central corneal thickness greater than 600 μm in either eye. Subjects with any condition that prevents reliable applanationtonometry 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 active optic disc hemorrhage. Subjects with a history of central/branch retinal vein or artery occlusion. Subjects with a history of macular edema. Subjects with very narrow angles 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 with any intraocular infection or inflammation within 3 months prior to Visit 1 (Screening). Subjects with a history of ocular laser surgery within the 3 months prior to Visit 1 (Screening). Subjects with a history of incisional ocular surgery or severe trauma within 3 months prior to Visit 1 (Screening).

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Timolol Maleate<br>Timolol maleate ophthalmic solution 0.5% administered 1 drop BID once in morning and once in the evening for 4 weeks. | Drug: Timolol maleate<br>* Topical ophthalmic solution<br>|
| Experimental: BOL-303259-X<br>BOL-303259-X topical ophthalmic solution administered 1 drop QD in the evening for 4 weeks. | Drug: BOL-303259-X<br>* Topical ophthalmic solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 Hour IOP | Supine intraocular pressure (IOP) measured in the study eye following 4 weeks of treatment | after 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour Ocular Perfusion Pressure | Sitting Ocular Perfusion Pressure = 95/140 x mean arterial blood pressure - IOP; Supine Ocular Perfusion Pressure = 115/130 x mean arterial blood pressure - IOP; the nocturnal time frame encompassed measures taken at 10pm, 12am, 2am and 4 am; whereas the diurnal time frame encompassed measures taken at 6am, 8am, 10am, 12pm, 2pm, 4pm, 6pm, and 8pm. | after 4 weeks of treatment | 
| IOP Area Under the Curve Over 24 Hours | The Area Under the Curve(AUC) is the weighted average of IOP over all 24-hour IOP assessment times (2pm, 4pm, 6pm, 8pm, 10pm, 12am, 2am, 4am, 6am, 8am, 10am, 12pm). The AUC was calculated using the trapezoidal rule. | after 4 weeks of treatment |