PRO-122 Versus Concomitant Therapy in Subjects With Uncontrolled Primary Open-angle Glaucoma (PRO-122LATAM)
- Conditions
- Primary Open-angle Glaucoma
- Interventions
- Other: Placebo1Drug: Dorzolamide-Timolol OphthalmicOther: Placebo 2Drug: Krytantek
- Registration Number
- NCT03193333
- Lead Sponsor
- Laboratorios Sophia S.A de C.V.
- 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
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 51
- 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.
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Concomitant triple therapy group Timolol eye drops 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 Concomitant triple therapy group Dorzolamide-Timolol Ophthalmic 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 Krytantek Ofteno Group Placebo1 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 PRO-122 group Placebo 2 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 Concomitant triple therapy group Brimonidine Ophthalmic Solution 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 Krytantek Ofteno Group Krytantek 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 PRO-122 group Placebo1 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 Krytantek Ofteno Group Placebo 2 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 PRO-122 group PRO-122 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
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
MD. Sandra Belalcazar Rey
🇨🇴Bogotá, Bogotá D.C., Colombia
MD. Victoria Eugenia Sanchez Castellanos
🇲🇽Zapopan, Jalisco, Mexico