Safety and Tolerability of the Preservative-free Ophthalmic Solution PRO-122 Compared With Krytantek Ofteno®

Study Overview
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Brief Summary
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Therapeutic indication: Ocular hypotensive Use: Primary open-angle glaucoma and ocular hypertension. Objectives: To evaluate the safety and tolerability of the preservative-free formulation PRO-122 manufactured by Sophia Laboratories, S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis: The ophthalmic solution PRO-122 presents a profile of safety and tolerability similar to Krytantek Ofteno®, in healthy subjects. Methodology: Phase I clinical trial, controlled, parallel group, double blind, randomized. Number of patients: n=24 12 subjects per group (both eyes). Main inclusion criteria:Clinically healthy subjects.

Detailed Description
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Number of patients: n = 24 12 subjects per group (both eyes). Main inclusion criteria: Clinically healthy subjects. Treatment duration: 7 days. Duration of subject in the study: 15 to 22 days. Adverse events will be reported and cataloged based on the MedDRA dictionary and will be reported to the corresponding regulatory entity. The sponsor will carry out monitoring or quality visits to the research sites where it corroborates the information of the source documents and will contrast them with the information presented in the electronic CRF. Electronic case report forms will be evaluated by the clinical research associate and the clinical team of the sponsor (medical ophthalmologist researcher and pharmacologist of clinical safety). Statistical methodology: The data will be expressed with measures of central tendency: mean and standard deviation for the quantitative variables. The qualitative variables will be presented in frequencies and percentages. The statistical analysis will be carried out by means of the Mann-Whitney U test for the quantitative variables for the difference between the groups. The difference between the qualitative variables will be analyzed by means of X2 (Chi2). An alpha ≤ 0.05 will be considered significant.

Official Title
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Phase I Clinical Study, to Evaluate the Safety and Tolerability of the Preservative-free Ophthalmic Solution PRO-122 Compared With Krytantek Ofteno®, Elaborated by Sophia Laboratories, S.A. of C.V. on the Ocular Surface of Ophthalmologically and Clinically Healthy Subjects

Conditions
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Glaucoma

Intervention / Treatment
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* Drug: PRO-122
* Drug: Krytantek Ofteno®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Clinically healthy Ability to give your signed informed consent, and show willingness to comply with study procedures and to modify your lifestyle activities (Section 6.2.2) Age between 18 to 45 years. Indistinct sex. Women must ensure a hormonal contraceptive method or intrauterine device during the study period. Blood tests: within normal parameters or with a range of ± 20% as long as the subject is clinically healthy. Blood count (BH): Hemoglobin, erythrocytes, hematocrit, total leukocytes, platelets, mean corpuscular volume and mean corpuscular hemoglobin. Blood chemistry of three elements (QS): Glucose, urea and creatinine. Liver function tests (PFH): Aspartate Aminotransferase and Alanine Aminotransferase, total bilirubin, direct and indirect. Visual ability 20/30 or better in both eyes. Vital signs within normal parameters. Intraocular pressure ≥10 and ≤ 21 mmHg. Exclusion Criteria: Users of topical ophthalmic products of any kind. Users of medicines, or herbal products, by any other route of administration, with the exception of hormonal contraceptives in the case of women. Women who are pregnant or breastfeeding. Participation in clinical research studies 90 days prior to inclusion in the present study. Previous participation in this same study. Users of contact lenses. History of any chronic-degenerative disease. Inflammatory or infectious disease, active at the time of study entry. Injuries or traumatisms not resolved at the time of admission to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Phase I clinical trial, controlled, parallel group, double blind, randomized.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-122<br>- Dosage: 1 drop every 12 hours, in both eyes | Drug: PRO-122<br>* PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. Route of administration: topical ophthalmic.<br>* Other names: Krytantek Ofteno® Preservative Free;|
| Active Comparator: Krytantek Ofteno®<br>- Dosage: 1 drop every 12 hours, in both eyes | Drug: Krytantek Ofteno®<br>* - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.<br>* Other names: dorzolamide 2%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | primary security variable the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent. it will be evaluated by the number of reported cases per group. | during the 14 days of evaluation, including the safety call (day 14) | 
| Eye Comfort Index | It is a questionnaire designed to measure the irritation of the ocular surface with Rasch analysis to produce estimates on a linear scale of intervals (ratings: 0-100).The Eye comfort index contains items that focus on the discomfort associated with alterations of the ocular surface. Values closer or equal to one hundred (100) correspond to greater discomfort, while values closer or equal to zero (0) correspond to greater comfort. | will be evaluated at the end of the treatment, at the final visit (day 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Eyes With Epithelial Defects by Grade | The epithelial defects will be evaluated by means of two stains, green lissamine and fluorescein, it is a discrete variable that will be realized by direct observation, it will be staged according to the degrees of the oxford scale that go from 0 to 5 (0-V) according to its severity, where 0 is the normal lower limit and 5 the upper limit of defects. | will be evaluated at the end of the treatment, at the final visit (day 8) | 
| Visual Ability | The visual capacity variable will be reported using as a unit of measure a fraction, this is taken from a visual test with the Snellen primer, it is a Nominal type variable. where the optimal vision is 20/20 or 1.0 in decimal and the worst 20/200 or 0.1 in decimal number. For the appropriate management of the data, the result of the fraction obtained from the snellen scale is transformed to decimals, in this case subjects close to or equal to 1.0 have better visual acuity while subjects close to or equal to 0.1 have worse visual acuity. The decimal equivalence scale is the result of the division of the fraction obtained in the Snellen chart. where 20/20 = 1.0; Do not confuse with Logmar scale where 20/20 = 0.0 Equivalences Snellen Scale = decimals: 20/200=0.1, 20/100=0.2, 20/50=0.4, 20/40=0.5, 20/30=0.66, 20/25=0.8, 20/20=1.0, etc. | will be evaluated at the end of the treatment, at the final visit (day 8) | 
| Participants With Conjunctival Hyperemia (CH) by Grade | Conjunctival hyperemia will be evaluated as an ordinal variable, by direct observation and staged using the Efron scale as Normal / Very Light / Mild / Moderate / Severe. Based on this scale, the normal and mild stages are considered without pathologies or normal. Mild, moderate and severe are considered pathological. | will be evaluated at the end of the treatment, at the final visit (day 8) | 
| Participants With Chemosis | The chemosis will be evaluated, as a nominal variable, by direct observation and it will be staged as present and absent, where the normality is that said variable is absent. | will be evaluated at the end of the treatment, at the final visit (day 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glaucoma, Krytantek, Krytantek PF, PRO-122