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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: October 31, 2019

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.

Interventions

  • Drug: PRO-122
    • Posology: 1 drop every 12 hours for 90 days
  • Drug: Timolol eye drops
    • 1 drop every 12 hours for 90 days
  • Drug: Dorzolamide-Timolol Ophthalmic
    • 1 drop every 12 hours for 90 days
  • Drug: Brimonidine Ophthalmic Solution
    • 1 drop 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

Arms, Groups and Cohorts

  • 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
  • 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
  • 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

Clinical Trial Outcome Measures

Primary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Laboratorios Sophia S.A de C.V.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Leopoldo Baiza, MD, Study Director, Laboratorios Sophia S.A de C.V.
  • Overall Contact(s)
    • Ricardo Llamas, PhD, (33)30014200, ricardo.llamas@sophia.com.mx

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.