Changes made included the following: - Replaced “BOL-303259-X latanoprostinod” with “BOL 303259-X” since latanoprostinod is not an approved compound name. - Increased the baseline IOP in the study to be able to examine the difference between the IOP-lowering effects of the test article and the active comparator, one of the 3 mean/median IOP measurements in Inclusion Criterion was changed from ≥24 mmHg to ≥26 mmHg at a minimum of 1 time point in the same eye. - Removed the requirement for a negative urine pregnancy test at Visit 2 (mid-washout). - Maximum central corneal thickness was changed from 600 μm to 590 μm in Exclusion Criterion to avoid enrolling subjects with artificially highly IOPs. - Added “in either eye” to Exclusion Criterion to clarify that subjects with very narrow angles, angle closure, congenital and secondary glaucoma, and history of angle closure in either eye should be excluded. - Removed instructions to perform vital signs in the standing position. - Added a description of the subject dosing instruction sheet. - Removed events occurring from any failure of expected pharmacological action from the definition of an AE since this was a dose-ranging study and collection of lack of effect events was not required. - Revised serious adverse event definition to be more consistent with global standards. - Clarified that non-serious AEs that were ongoing upon early discontinuation from the study were also to be followed by the Investigator for 30 days after the subject exited the study. - Removed the Snellen fraction information from the Recording and Scoring of logMar values.

Changes included the following: - Revised Inclusion Criterion to indicate that the mean/median IOP should be ≤32 mmHg in both eyes at all 3 measurement time points. - Revised Exclusion Criterion to include subjects expected to require treatment with systemic corticosteroids. - Removed performing vital signs in the standing position from the Study Procedures section in the synopsis and removed the description of collecting measurements for different body postures in Appendix. - Clarified that the unmasked designee should weight study medication bottles and dispense study medication. - Clarified that the comparator’s screw cap was turquoise in the US and white in the EU. - Clarified that if the 2 systolic or diastolic values of the blood pressure measurements differed by more than 5 mmHg, a third reading should be taken and the average of the 3 measurements should be averaged.

Changes included the following: - Revised the maximum allowed central corneal thickness in either eye in Exclusion Criterion from 590 μm to 600 μm. After review of the screening failures in this study, a high rate of exclusion was shown to be due to the maximum allowed central corneal thickness of 590 μm. Although increased central corneal thickness may give artificially high IOP measurements, an increase of 10 μm is very small and its effect on IOP would be minimal and negligible. This change did not affect the study objective or endpoints and did not create any safety concerns for the study subjects. - Removed calcium channel blockers as an example medication that could interact with the safety or efficacy of a NO-donating compound from the disallowed therapies in Exclusion Criterion. The subject population in this study was older by nature, tended to have hypertension, and had higher rates of calcium channel blocker use, as shown during screening. Since the interim safety data review of the enrolled and dosed subjects showed no safety signals for hypotension, the study drug was not expected to potentiate the hypotensive effect of calcium channel blockers used in the study. To be able to have a good representation of the general glaucoma population, calcium channel blocker use was permitted in the study.