PRO-122 Versus Concomitant Therapy in Subjects With Uncontrolled Primary Open-angle Glaucoma (PRO-122LATAM)

Objectives: To evaluate the non-inferiority in the intraocular pressure decrease of the preservative-free ophthalmic solution PRO-122, manufactured by Laboratorios Sophia S.A. de C.V., versus concomitant therapy in subjects with uncontrolled primary open-angle glaucoma and/or IOP.

Hypothesis: The mean (average) value of the IOP final absolute reduction in the experimental group (PRO-122) is not lower, considering a lower limit of 1 mmHg, compared to the IOP mean absolute reduction of the standard group (concomitant therapy).

Methodology: A non-inferiority, phase III, double-blind, randomized, controlled, parallel, clinical trial

Number of patients: 51 subjects divided into 3 groups (17 subjects per group)

Diagnosis and main inclusion criterion:

Diagnosis: Primary open-angle glaucoma or ocular hypertension

Main criteria:

* Patients of either sex
* Average intraocular pressure (IOP) ≤ 36 mm/Hg
* Previous management with ocular hypotensive medications ≥ 2 months, without achieving control (target IOP)
* Age ≥ 18 years
* Informed consent

Test product, dosage and route of administration:

* PRO-122. Preservative-free ophthalmic solution of timolol 0.5% / brimonidine 0.2% / dorzolamide 2% Manufactured by Laboratorios Sophia, S.A. de C.V., Zapopan, Jalisco, Mexico. + Placebo + Placebo
* Dosage: 1 drop every 12 hours
* Route of administration: ophthalmic

Treatment duration: 90 days

Evaluation criteria:

Efficiency (non-inferiority):

* IOP decrease

Safety:

* Best corrected visual acuity
* Cup-to-disc ratio
* Visual fields determined by computerized perimetry
* Central corneal thickness determined by pachymetry
* Ocular surface integrity, including:

  * Conjunctival hyperemia
  * Chemosis
  * Fluorescein staining
* Density of goblet cells
* Adverse events

Tolerability:

* Ocular comfort index

Statistical methodology:

The data will be expressed with measures of central tendency: mean and standard deviation for quantitative variables. The qualitative variables will be presented in frequencies and percentages. Statistical analysis will be done by means of a Kruskal-Wallis test for quantitative variables. The difference between qualitative variables will be analyzed using an square chi An alpha ≤ 0.05 would be considered as significant.

Eligibility Criteria:
Inclusion Criteria:

* Signed informed consent
* Age greater or equal to 18 years
* Both sexes
* Women of childbearing age with birth control method
* Diagnosis of Primary open-angle glaucoma (according to the Guidelines of the Preferred Practice Pattern of the American Academy of Ophthalmology) or ocular hypertension (OHT)
* Intraocular pressure (IOP) not controlled with dual therapy according to the principal investigator (PI) judgment.
* IOP on the selection visit at 9 am, after the washing period, from 21 - 36 mmHg in at least one eye.

Exclusion Criteria:

General criteria

* Pregnant, breastfeeding or planning to get pregnant women.
* Women of childbearing age and who do not intake a hormonal contraceptive method, intrauterine device or bilateral tubal obstruction.
* Participation in another clinical research study greater or equal 30 days before the screening visit.
* People who cannot comply with their attendance at appointments or with all the - Protocol requirements

Medical and therapeutic criteria:

* Anterior chamber angle grade less than 2 of Shaffer rating.
* Excavation of optic nerve greater than 0.80 horizontal or vertical (ratio cup-disc)
* Serious loss of central visual field in any eye (sensitivity less or equal to 10 decibels in greater or equal to 2 of 4 points of the visual field test close to the fixation point)
* People not able to safely suspend ocular hypotensives drug products for the washout period according to the PI judgement.
* Chronic, recurrent, or active ocular inflammatory diseases (e.g. uveitis, scleritis, keratitis, herpetic) in any eye.
* Eye trauma less or equal to 6 months prior to the study
* Eye infection / inflammation less or equal to 3 months prior to the study
* Clinically significant or progressive retinal disease (e.g. degenerations, diabetic retinopathy, retinal detachment)
* Ability Visual 20/200 or worse in any of the eyes.
* Subject with only one eye
* Eye diseases that contraindicate the use of Beta-blocker (BB) Alpha-adrenergic agonist (AA) or Carbonic anhydrase inhibitors (CAIs)
* Intraocular surgery less or equal to 6 months prior to the study
* Laser intraocular surgery less or equal to 3 months prior to the study
* Any abnormality preventing reliable applanation tonometry
* Unstable or uncontrolled cardiovascular disease
* Chronic pulmonary disease (e.g. bronchial asthma)
* Any condition or illness that do not fit the subject for the study according to the PI judgment.
* Use of high doses of salicylate (1 g daily) less or equal to4 weeks before the eligibility visit
* In treatment with psychotropic medications that increase the adrenergic response
* Known hypersensitivity to BB medications (e.g. timolol), AA (e.g. brimonidine) and CAI (e.g. dorzolamide), sulfonamide derivatives, or any of the components of the study drugs
* Concomitant use of monoamine oxidase inhibitors
* Systemic or topical use of corticosteroids