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

Sponsor

Laboratorios Sophia S.A de C.V. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03193333

Collaborator

(none)

Enrollment

Locations

Arms

58.8

Anticipated Duration (Months)

25.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Primary Open-angle Glaucoma	Drug: PRO-122 Drug: Timolol eye drops Drug: Dorzolamide-Timolol Ophthalmic Drug: Brimonidine Ophthalmic Solution Other: Placebo1 Other: Placebo 2 Drug: Krytantek	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

51 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Double (Participant, Investigator)

Masking Description:

Blinding will be performed by the personnel assigned by the Laboratorios Sophia S.A. de C.V. Clinical Operations Management. The blinding will consist in the elimination of the primary label (commercial) for Krytantek Ofteno® and the triple concomitant therapy and the placement of a label identical to those of the other interventions. Since the bottles in which Krytantek Ofteno® and the concomitant therapies are different in color and cap shape to the ones used for the placebo and the PRO-122, a masking will be performed in the primary packaging, which shall be identical for all three interventions.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 6, 2017

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

intraocular pressure (IOP) [90days]
Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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