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

• BOL-303259-X (Drug), also known as latanoprostene bunod: ophthalmic solution, various concentrations, once daily (QD) 28 days
• Latanoprost (Drug), also known as Xalatan: 0.005% ophthalmic solution, QD 28 days

Primary outcomes

• Change in Mean Diurnal IOP at Visit 6 (Day 28) [Baseline and 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

Secondary outcomes

• Change in Mean Diurnal IOP at Visits 4,5, and 7 [Baseline and Visit 4 (Day 7), Visit 5 (day 14), and Visit 7 (Day 29)]: Determine the most effective drug concentration(s) of BOL-303259-X in the reduction of intraocular pressure (IOP) and compared to latanoprost
• IOP </=18mm Hg [Visit 4 (Day 7), Visit 5 (day 14), Visit 6 (Day 28) and Visit 7 (Day 29)]: Determine the number of subjects with mean diurnal IOP </=18 mm Hg with BOL-303259-X versus latanoprost ophthalmic solution
• Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28) [baseline and 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)
• Change in IOP at Specified Time Points (8 AM, 12 PM, 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)]: 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)

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Change in Mean Diurnal IOP at Visit 6 (Day 28) (Primary), Mean, mm Hg: BOL-303259-X 0.006% -7.829 +/- 2.823; BOL-303259-X 0.012% -8.295 +/- 2.864; BOL-303259-X 0.024% -8.952 +/- 3.337; BOL-303259-X 0.040% -8.894 +/- 2.666; Latanoprost -7.800 +/- 2.834
• Change in Mean Diurnal IOP at Visits 4,5, and 7 (Secondary), Mean, mm Hg: BOL-303259-X 0.006% -6.850 +/- 2.768; BOL-303259-X 0.012% -7.707 +/- 3.192; BOL-303259-X 0.024% -8.230 +/- 3.286; BOL-303259-X 0.040% -8.456 +/- 2.892; Latanoprost -7.325 +/- 2.699
• IOP </=18mm Hg (Secondary), Count of participants, Participants: BOL-303259-X 0.006% 30; BOL-303259-X 0.012% 37; BOL-303259-X 0.024% 47; BOL-303259-X 0.040% 46; Latanoprost 29
• Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28) (Secondary), Mean, mm Hg: BOL-303259-X 0.006% -8.42 +/- 3.69; BOL-303259-X 0.012% -8.91 +/- 3.24; BOL-303259-X 0.024% -9.46 +/- 4.01; BOL-303259-X 0.040% -9.61 +/- 2.95; Latanoprost -8.76 +/- 3.24
• Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) (Secondary), Mean, mm Hg: BOL-303259-X 0.006% -7.203 +/- 3.634; BOL-303259-X 0.012% -8.396 +/- 3.935; BOL-303259-X 0.024% -8.667 +/- 3.827; BOL-303259-X 0.040% -8.869 +/- 3.384; Latanoprost -8.125 +/- 2.826

Adverse events

Time frame: The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7).

Serious adverse events by term

Other adverse events by term

• Results publication: Weinreb RN, Ong T, Scassellati Sforzolini B, Vittitow JL, Singh K, Kaufman PL; VOYAGER study group. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015 Jun;99(6):738-45. doi: 10.1136/bjophthalmol-2014-305908. Epub 2014 Dec 8. PMID 25488946

• Rabia Ozden, MD, Study director, Bausch & Lomb Incorporated