A PHASE III, MULTICENTRE, RANDOMISED, INVESTIGATOR-MASKED, CROSS-OVER, COMPARATIVE, NON-INFERIORITY TRIAL OF GENERIC LATANOPROST + TIMOLOL (50μG + 5MG)/ML EYE DROPS, SOLUTION (POLPHARMA S.A.) COMPARED TO XALACOM® (LATANOPROST 0.005 % OPHTHALMIC SOLUTION & TIMOLOL 0.5% FIXED COMBINATION, PFIZER) IN PATIENTS WITH OCULAR HYPERTENSION OR PRIMARY OPEN ANGLE GLAUCOMA.

INTERVENTION: Product Name: latanoprost + timolol (50 µg + 5 mg)/ml oldatos szemcsepp (Polpharma S.A.), preservative free Pharmaceutical Form: Eye drops, solution INN or Proposed INN: Latanoprost and Timolol CAS Number: 130209‐82‐4 Other descriptive name: LATANOPROST and Timolol Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Trade Name: Xalacom® Product Name: Xalacom® (latanoproszt 0,005% és timolol 0,5% fix kombinációs oldatos szemcsepp, Pfizer). Pharmaceutical Form: Eye drops, solution CONDITION: Ocular hypertension and open angle glaucoma ; MedDRA version: 20.0 Level: PT Classification code 10030043 Term: Ocular hypertension System Organ Class: 10015919 ‐ Eye disorders ; MedDRA version: 20.0 Level: PT Classification code 10030348 Term: Open angle glaucoma System Organ Class: 10015919 ‐ Eye disorders Therapeutic area: Diseases [C] ‐ Eye Diseases [C11] PRIMARY OUTCOME: Main Objective: PRIMARY OBJECTIVE; The primary objective is to evaluate the efficacy of the generic Latanoprost + Timolol (50µg + 5mg)/ml eye drops, solution (Polpharma S.A.; test product) in lowering IOP when compared to the originator Xalacom® (latanoprost 0.005% & timolol 0.5% fixed combination ophthalmic solution, Pfizer; reference product). Primary end point(s): PRIMARY ENDPOINT; Non‐inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP in the study eye at baseline (measured at 8 am, 12 pm and 4 pm on the day before treatment initiation at 8 am the following day) on Day 1 and on Day 29 (before treatment at 8 am, and 4 and 8 hours after the first measurement. IOP will be assessed using the Goldmann applanation tonometry. Secondary Objective: Secondary Objective(s); • To compare the ocular tolerance of the test and reference products using an ocular comfort level score.; • To compare the levels of conjunctival hyperaemia induced by test product and reference product.; • To evaluate safety in general determined by vital signs and the incidence and nature of AEs of the test product compared to the reference product.; • To evaluate the usability of the test product delivery device by comparison with the reference product delivery device. Timepoint(s) of evaluation of this end point: Day1 versus Day29 SECONDARY OUTCOME: Secondary end point(s): SECONDARY ENDPOINTS; Efficacy; Non‐inferiority of the test product when compared to the reference product with respect to the differences in the mean IOP in the study eye at baseline for each of the three measurement time points before and after treatment.; ; Ocular Tolerance; • Difference between the investigational products with respect to ocular comfort level score at baseline (Day 1) and Day 29; • Difference between the investigational products with respect to conjunctival hyperaemia at baseline (Day 1) and Day 29.; ; Safety; • Difference between the investigational products with respect to general safety as assessed by vital signs and the incidence and nature of adverse events.; ; Usability; • Evaluation if usability of the test product delivery device by comparison with the reference product delivery device. Timepoint(s) of evaluation of this end point: Day 1 vs Day 29 INCLUSION CRITERIA: INCLUSION CRITERIA • Ocular hypertension or primary open angle glaucoma in at least one eye: mean diurnal IOP measured on Day 1 before treatment at 8 am, 12 pm and 4 pm on the day must be higher than or equal to 22 mmHg, and lower than or equal to 34 mmHg (untreated, i.e. after washout). • Not on any ophthalmic pressure‐lowering medication, or able to be withdrawn from current pressure‐lowering medications for the washout periods as defined in this clinical trial protocol. • No clinically significant or progressive retinal disease. • No concomitant use of any topical ophthalmic medication other than artificial tears • No ocular glucocorticoids in the previous 3 months • No concomitant use of any medication that may increase adrenergic activity, i.e. psychotropic substances such as amitriptyline • No systemic medication that may alter IOP in the previous 30 days (e.g. beta blockers, calcium channel blockers, ACE inhibitors, prostaglandi