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

• BOL-303259-X (Drug): BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning
• Timolol (Drug): Timolol will be administered BID once in the morning and once in the evening.
• BOL-303259-X (Drug): All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).

Primary outcomes

• Mean IOP [8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)]: Mean intraocular pressure (IOP) in the 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).

Secondary outcomes

• IOP ≤ 18 mm Hg [8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)]: Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months
• IOP Reduction ≥ 25% [8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)]: Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months

Other outcomes

• Number of Participants With Ocular and Systemic Adverse Events [6 months]: Following assessments through 3 months (Visit 6), all participants, irrespective of previous randomization, converted to a single open label safety arm receiving BOL-303259-X QD in the evening for an additional 3 months through Visit 7. Adverse events were recorded throughout the comparative efficacy phase and open label extension phase.

Sex: All, ages: 18 Years to any

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).

Participant flow

Outcome results

• Mean IOP (Primary), Least squares mean, mm Hg: BOL-303259-X 19.17 +/- 3.748; Timolol 19.61 +/- 3.092 (p 0.216)
• IOP ≤ 18 mm Hg (Secondary), Count of participants, Participants: BOL-303259-X 49; Timolol 15 (p 0.084)
• IOP Reduction ≥ 25% (Secondary), Count of participants, Participants: BOL-303259-X 86; Timolol 25 (p 0.007)
• Number of Participants With Ocular and Systemic Adverse Events (Other pre specified), Count of participants, Participants: BOL-303259-X 36; Timolol 18; BOL-303259-X Safety Extension Phase 23

Adverse events

Time frame: 6 months

Serious adverse events by term

Other adverse events by term

• Results publication: Medeiros FA, Martin KR, Peace J, Scassellati Sforzolini B, Vittitow JL, Weinreb RN. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study. Am J Ophthalmol. 2016 Aug;168:250-259. doi: 10.1016/j.ajo.2016.05.012. Epub 2016 May 20. PMID 27210275
• Results publication: Weinreb RN, Liebmann JM, Martin KR, Kaufman PL, Vittitow JL. Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings. J Glaucoma. 2018 Jan;27(1):7-15. doi: 10.1097/IJG.0000000000000831. PMID 29194198

• Jason Vittitow, Study director, Bausch & Lomb Incorporated