Safety and Tolerability of the Ophthalmic Solution PRO-179 Compared With Travatan®

Study Overview
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Brief Summary
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Phase I clinical study, to evaluate the safety and tolerability of the ophthalmic solution PRO-179 compared with Travatan®, on the ocular surface of clinically healthy subjects. Goals: To evaluate the safety and tolerability of the formulation PRO-179 manufactured by Sophia Laboratories S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis:The ophthalmic solution PRO-179 presents a profile of safety and tolerability similar to Travatan® in healthy subjects. Methodology: Clinical trial Phase I, controlled, of parallel groups, double blind, with randomization.

Detailed Description
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Number of patients: n= 24, 12 subjects per group (both eyes). Main inclusion criteria: Clinically healthy subjects. duration: 10 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) or Fisher's exact. 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 Ophthalmic Solution PRO-179 Compared With Travatan®, on the Ocular Surface of Clinically Healthy Subjects.

Conditions
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Glaucoma

Intervention / Treatment
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* Drug: PRO 179
* Drug: Travatan 0.004 % Ophthalmic Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be clinically healthy. Have the ability to give their signed informed consent and show willingness to comply with the study procedures Have an age between 18 to 45 years. Indistinct sex. Women should ensure the continued use of a hormonal contraceptive method or intrauterine device (IUD) during the study period. Present 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. Present visual ability 20/30 or better in both eyes. Present vital signs within normal parameters. Present intraocular pressure ≥10 and ≤ 21 mmHg. Exclusion Criteria: Be a user of topical ophthalmic products of any kind. Be a user of medicines, or herbal products, by any other route of administration, with the exception of hormonal contraceptives in the case of women. In case of being a woman, being pregnant or breastfeeding. Have participated in clinical research studies 90 days prior to inclusion in the present study. Have previously participated in this same study. Be a user of contact lenses and can not suspend their use during the study. That they can not follow the lifestyle considerations described in section 6.2.2 Having started the use of hormonal contraceptives or IUD, 30 days prior to inclusion in the present study. Having a history of any chronic-degenerative disease. Present inflammatory or infectious disease, active at the time of admission to the study. Present injuries or unresolved traumas at the time of entering the study. Having the antecedent of any type of eye surgery. Having undergone surgical procedures, not ophthalmological, in the last 3 months.

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: double blind, with randomization.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-179<br>Dosage: 1 drop every 24 hours, at night, in both eyes. | Drug: PRO 179<br>* Generic name: Travoprost Distinctive denomination: Bristrio® (PRO-179) Active principles: Travoprost 0.004%. Pharmaceutical form: Ophthalmic solution Presentation: multi-dose dropper bottle, 2.5 milliliters. Prepared by: Sophia Laboratories, S.A. of C.V. Description of the solution: transparent solution, free of visible particles. Description of container: White bottle with 5 milliliters capacity, made of low density polyethylene.<br>* Other names: Travoprost 0.004% ophthalmic solution;|
| Active Comparator: Travatan®<br>Dosage: 1 drop every 24 hours, at night, in both eyes. | Drug: Travatan 0.004 % Ophthalmic Solution<br>* Generic name: Travoprost Distinctive denomination: Travatan® Active ingredients: Travoprost 0.004% Pharmaceutical form: Ophthalmic solution. Presentation: multi-dose dropper bottle, 2.5 milliliters. Prepared by: Alcon Laboratories Inc. Description of the solution: transparent solution, free of visible particles. Consult information to prescribe.<br>* Other names: Travoprost 0.004% ophthalmic solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 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.(0: None discomfort, 100: high discomfort). | will be evaluated at the end of the treatment, at the final visit (day 11) | 

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, lissamine green 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 11) | 
| 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 and the worst vision is 20/200, higher values represent a worst vision. The result of the Snellen chart has equivalents in an international logarithmic system called Logmar (logarithm of the minimum angle of resolution) for better understanding. Snellen Scale: 20/200, 20/100, 20/50, 20/40, 20/30, 20/25, 20/20, 20/15, 20/12, 20/10. Snellen / LogMAR equivalences: 20/200= 1.0, 20/100=0.7, 20/50=0.4, 20/40=0.3, 20/30=0.2, 20/25=0.1, 20/20=0.0, 20/15=0.13, 20/12=0.2, 20/10=-0.3, etc. | will be evaluated at the end of the treatment, at the final visit (day 11) | 
| Percentage of Eyes 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 11) | 
| Number of Eyes of 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 11) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Travoprost, ophthalmic solution, Prostaglandin Analogues, Antiglaucoma drugs, glaucoma