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

A Non-inferiority in the Intraocular Pressure Decrease of the Preservative-free Ophthalmic Solution PRO-122 Versus Concomitant Therapy in Subjects With Uncontrolled Primary Open-angle Glaucoma

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.

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