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

Study Overview

• Status: Recruiting
• Conditions: Primary Open-angle Glaucoma
• Intervention / Treatment: Drug: PRO-122; Other: Placebo1; Other: Placebo 2; Drug: Timolol eye drops; Drug: Dorzolamide-Timolol Ophthalmic; Drug: Brimonidine Ophthalmic Solution; Drug: Krytantek

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ricardo Llamas, PhD; Phone Number: 1259 (33)30014200; Email: ricardo.llamas@sophia.com.mx
• Study Contact Backup: Name: Oscar Olvera, MD; Phone Number: 1074 (33)30014200; Email: oscar.olvera@sophia.com.mx

Study Locations

• Colombia
  • Bogotá D.C.
    • Bogotá, Bogotá D.C., Colombia
      • Recruiting
      • MD. Sandra Belalcazar Rey
      • Contact: Mariana Cabrera, MD; Phone Number: 1605 +5713487333
      • Contact: Claudia Carbajal, BD; Phone Number: 1605 +5713487333
• Mexico
  • Jalisco
    • Zapopan, Jalisco, Mexico, 44960
      • Recruiting
      • MD. Victoria Eugenia Sanchez Castellanos
      • Contact: Victoria Sanchez Castellanos, MD; Phone Number: +5213339152222; Email: victoriaoftalmo@hotmail.com
      • Contact: Miguel Montes Salcedo, MD; Phone Number: +5213339152222; Email: doctorlasik@yahoo.com.mx

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRO-122 group; 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; Posology: 1 drop every 12 hours for 90 days; Other Names: krytantek PF (Timolol, Brimonidine, Dorzolamide); Other: Placebo1; 1 drop of each dropper bottle every 12 hours for 90 days; Other: Placebo 2; 1 drop of each dropper bottle every 12 hours for 90 days
Active Comparator: Concomitant triple therapy group; 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; 1 drop every 12 hours for 90 days; Other Names: Concomitant triple therapy; Drug: Dorzolamide-Timolol Ophthalmic; 1 drop every 12 hours for 90 days; Other Names: Concomitant triple therapy; Drug: Brimonidine Ophthalmic Solution; 1 drop every 12 hours for 90 days; Other Names: Concomitant triple therapy
Active Comparator: Krytantek Ofteno Group; 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; 1 drop of each dropper bottle every 12 hours for 90 days; Other: Placebo 2; 1 drop of each dropper bottle every 12 hours for 90 days; Drug: Krytantek; Posology: 1 drop every 12 hours for 90 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Laboratorios Sophia S.A de C.V.
• Investigators: Study Director: Leopoldo Baiza, MD, Laboratorios Sophia S.A de C.V.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2017
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: glaucoma; timolol; primary open-angle glaucoma; brimonidine; dorzolamide; Ophthalmic antihypertensives; Krytantek Ofteno®.
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Glaucoma, Open-Angle; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Carbonic Anhydrase Inhibitors; Pharmaceutical Solutions; Timolol; Brimonidine Tartrate; Dorzolamide; Ophthalmic Solutions
• Other Study ID Numbers: SOPH122-0316/III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No