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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Primary Open-angle Glaucoma

Intervention / Treatment
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* Drug: PRO-122
* Drug: Timolol eye drops
* Drug: Dorzolamide-Timolol Ophthalmic
* Drug: Brimonidine Ophthalmic Solution
* Other: Placebo1
* Other: Placebo 2
* Drug: Krytantek


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A non-inferiority, phase III, double-blind, randomized, controlled, parallel, clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-122 group<br>To validate the 3 flasks of the triple therapy will be used 1 bottle with the three active principles (PRO-122) and two placebos and thus comply with the masking. Drug substances: Timolol 5 mg/mL, brimonidine 2 mg/mL and dorzolamide 20 mg/mL. preservative free. Pharmaceutical form: Ophthalmic solution Made by: Laboratorios Sophia, S.A. de C.V. Posology: 1 drop every 12 hours for 90 days Description of the solution: clear, visibly particle free, slightly yellow solution, preservative free Package description: 5 m multidose dropper bottle. Placebo (for Two pieces of approved placebo. Administered in 2 multidose dropper bottles. Posology: 1 drop of each dropper bottle every 12 hours for 90 days | Drug: PRO-122<br>* Posology: 1 drop every 12 hours for 90 days<br>* Other names: krytantek PF (Timolol, Brimonidine, Dorzolamide);Other: Placebo1<br>* 1 drop of each dropper bottle every 12 hours for 90 days<br>Other: Placebo 2<br>* 1 drop of each dropper bottle every 12 hours for 90 days<br>|
| Active Comparator: Concomitant triple therapy group<br>Imot Ofteno Drug substance: Timolol 5 mg/mL Pharmaceutical form: Ophthalmic solution Made by Laboratorios Sophia S.A. de C.V. Alphagan Drug substance Brimonidine 2 mg/mL Pharmaceutical form: Ophthalmic solution Made by: Allergan, Inc. Trusopt Drug substance: Dorzolamide 20 mg/mL Pharmaceutical form: Ophthalmic solution Made by: Merck Sharp and Dohme Corp. Posology: 1 drop every 12 hours for 90 days | Drug: Timolol eye drops<br>* 1 drop every 12 hours for 90 days<br>* Other names: Concomitant triple therapy;Drug: Dorzolamide-Timolol Ophthalmic<br>* 1 drop every 12 hours for 90 days<br>* Other names: Concomitant triple therapy;Drug: Brimonidine Ophthalmic Solution<br>* 1 drop every 12 hours for 90 days<br>* Other names: Concomitant triple therapy;|
| Active Comparator: Krytantek Ofteno Group<br>To validate the three flasks of the triple therapy will be used 1 bottle with the three active principles (Krytantek) and two placebos and thus comply with the masking. Drug substances: Timolol 5 mg/mL, brimonidine 2 mg/mL and dorzolamide 20 mg/mL. Pharmaceutical form: Ophthalmic solution Made by: Laboratorios Sophia, S.A. de C.V. Posology: 1 drop every 12 hours for 90 days Description of the solution: clear, visibly particle free, slightly yellow solution Package description: 5 m multidose dropper bottle. Placebo (for two pieces of approved placebo. Administered in 2 multidose dropper bottles. Posology: 1 drop of each dropper bottle every 12 hours for 90 days | Other: Placebo1<br>* 1 drop of each dropper bottle every 12 hours for 90 days<br>Other: Placebo 2<br>* 1 drop of each dropper bottle every 12 hours for 90 days<br>Drug: Krytantek<br>* Posology: 1 drop every 12 hours for 90 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intraocular pressure (IOP) | Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg | 90days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glaucoma, primary open-angle glaucoma, Ophthalmic antihypertensives, Krytantek Ofteno®., timolol, brimonidine, dorzolamide