Safety and Tolerability of PRO-087 Versus Xyel Ofteno® and Systane Ultra®, on the Ocular Surface of Healthy Subjects

Study Overview
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Brief Summary
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Phase I clinical study, to evaluate the safety and tolerability of the preservative-free ophthalmic solution PRO-087 versus Xyel Ofteno® and Systane Ultra®, on the ocular surface of ophthalmological and clinically healthy subjects. Objective: To evaluate the safety and tolerability of the preservative-free formulation PRO-087 manufactured by Laboratorios Sophia S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis: The ophthalmic solution PRO-087 presents a profile of safety and tolerability similar to comparators in healthy subjects Methodology: Phase I clinical trial, controlled, of parallel groups, double blind, randomized, exploratory.

Detailed Description
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Phase I clinical study, to evaluate the safety and tolerability of the preservative-free ophthalmic solution PRO-087 versus Xyel Ofteno® and Systane Ultra®, on the ocular surface of ophthalmological and clinically healthy subjects. Objective: To evaluate the safety and tolerability of the preservative-free formulation PRO-087 manufactured by Laboratorios Sophia S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis: The ophthalmic solution PRO-087 presents a profile of safety and tolerability similar to comparators in healthy subjects Methodology: Phase I clinical trial, controlled, of parallel groups, double blind, randomized, exploratory. Study period: 3 to 4 months treatment duration: 10 days Number of patients: 30 subjects, divided into 3 groups,10 subjects (20 eyes) exposed by group. Diagnosis and main inclusion criteria: Systemically and ophthalmologically healthy subjects Signed informed consent. Age between 18 to 40 years Both genders Blood tests complete, blood count (BHC), three element blood chemistry (QS) and liver function tests, within normal parameters Visual capacity 20/30 or better Test product, dose and route of administration: - PRO-087. Chondroitin sulfate 0.18% / 0.1% sodium hyaluronate, ophthalmic solution preservative free. made by Laboratorios Sophia, S.A. of C.V., Zapopan, Jalisco, Mexico. Dosage: 1 drop 4 times a day during the waking period, both eyes Route of administration: topical ophthalmic. Reference product, dose and route of administration: Xyel Ofteno®. Xanthan gum 0.09% / Chondroitin sulfate 0.1% / preservative-free ophthalmic solution. made by Laboratorios Sophia, S.A. of C.V., Zapopan, Jalisco, Mexico. Dosage: 1 drop 4 times a day during the waking period, both eyes Route of administration: topical ophthalmic. Systane Ultra®. Polyethylene glycol 400 0.4%, propylene glycol 0.3%. made by Alcon Laboratories, Inc. Dosage: 1 drop 4 times a day during the waking period, both eyes Route of administration: topical ophthalmic. Evaluation criteria: Primary security outcome variables: Goblet cells density . Presence of adverse events. Intraocular pressure. Visual ability Laboratory tests Epithelial defects in cornea and conjunctiva. Ophthalmological signs: conjunctival hyperemia, chemosis. Secondary outcome variables: Tear film rupture time Life signs: heart rate, respiratory frequency systemic blood pressure. Subsequent segment Primary outcome variables of tolerability: Burning Foreign body sensation Itching Eye comfort index 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 through the Kruskal-Wallis test for quantitative variables. The difference between the qualitative variables will be analyzed by means of chi square (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-087 Versus Xyel Ofteno® and Systane Ultra®, on the Ocular Surface of Ophthalmologically and Clinically Healthy Subjects

Conditions
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Dry Eye Syndromes, Lubricant Allergy, Tear Disorder

Intervention / Treatment
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* Drug: PRO-087
* Drug: Systane Ultra
* Drug: Xyel Ofteno


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Systemically and ophthalmologically healthy subjects Signed informed consent. Age between 18 to 40 years. Both genders Blood tests [complete blood count (BHC), three element blood chemistry (QS) and liver function tests (PFH)] within normal parameters Visual capacity 20/30 or better Exclusion Criteria: Subjects with a history of hypersensitivity to any of the components of the research products. Subject users of topical ophthalmic medications of any pharmacological group. Subject users of medication by any other route of administration. Women who are pregnant or breastfeeding. Women without a history of hysterectomy, oophorectomy or hysterectomy, who do not ensure a hormonal contraceptive method or intrauterine device during the study period. Subjects with participation in clinical research studies 90 days prior to inclusion in the present study. Diagnosis of liver disease or triple the normal upper value of any of the following liver enzymes: aspartate transferase (AST), alanine transferase (ALT) or bilirubin. Inability to attend or answer the evaluations made in each of the visits. Positive smoking (specified as cigarette consumption regardless of quantity and frequency) Positive alcoholism (specified as the consumption of alcoholic beverages, regardless of quantity and frequency, during the study intervention period). Users of contact lenses.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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, of parallel groups, double blind, randomized, exploratory.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-087<br>Dosage: 1 drop in both eyes, 4 times a day during the waking period per 10 days Active principles: chondroitin sulfate 0.18%, sodium hyaluronate 0.1% ophthalmic solution made by Laboratorios Sophia, S.A. de C.V., transparent solution, free of visible particles in a sterile multi-dose bottle. | Drug: PRO-087<br>* The intervention period consists of a therapy with PRO-087administered 4 times a day in the waking period for 10 days. with a security call to day 13.<br>* Other names: humylub PF ophthalmic solution;|
| Active Comparator: Xyel Ofteno<br>Dosage: 1 drop in both eyes, 4 times a day during the waking period per 10 days, Active principles: Xanthan gum 0.9 mg, sodium chondroitin sulfate 1.0 ophthalmic solution made by Laboratorios Sophia, S.A. de C.V., transparent solution, free of visible particles in a sterile multi-dose bottle. | Drug: Xyel Ofteno<br>* The intervention period with active comparator drug consists of a therapy with Xyel administered 4 times a day in the waking period for 10 days. with a security call to day 13.<br>* Other names: Xanthan gum 0.9 mg, sodium chondroitin sulfate;|
| Active Comparator: Systane ultra<br>Dosage: 1 drop in both eyes, 4 times a day during the waking period per 10 days Active principles: Polyethylene glycol 400 0.4%, propyleneglycol 0.3%, Ophthalmic solution, multi-dose dropper bottle, made by Alcon Laboratories, Inc. | Drug: Systane Ultra<br>* The intervention period with active comparator drug consists of a therapy with systane administered 4 times a day in the waking period for 10 days. with a security call to day 13.<br>* Other names: Polyethylene glycol 400 0.4%, propyleneglycol 0.3%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Goblet Cell Density (GCD) | the cells will be measured per square millimeter, it is a continuous variable taken by means of cytology per impression, the normal value is higher than 500 cells per square millimeter | will be evaluated at the end of the treatment at the final visit (day 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of Adverse Events (AEs) | the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent. | during the 13 days of evaluation, including the safety call (day 13). | 
| Intraocular Pressure (IOP) | the intraocular pressure will be evaluated by means of the Goldman applanation tonometry whose unit of measurement is millimeters of mercury (mmHg), it is a continuous variable and its normality range is between 11 - 21 mmHg | will be evaluated at the end of the treatment at the final visit (day 10) | 
| Epithelial Defects (ED) | The epithelial defects will be evaluated by means of two stains, green lysine 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 10) | 
| Breakup Time (BUT) | breakup time lacrimal film is a continuous variable that will be measured in seconds, evaluating the time it takes to break it, is done by direct counting and the normality range and mayor to 10 seconds. | will be evaluated at the end of the treatment at the final visit (day 10) | 
| Conjunctival Hyperemia (CH) | Conjunctival hyperemia will be evaluated as an ordinal variable, by direct observation and staged using the Efron scale as Normal / Very mild / Mild / Moderate / Severe. Based on this scale, the normal and mild stages are considered without pathologies or normal. Moderate and severe are considered pathological. | will be evaluated at the end of the treatment at the final visit (day 10) | 
| 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 10) | 
| Ocular Burning (OB) | ocular burning is a nominal variable that will be evaluated by direct questioning to the research subject, then it will be staged according to the following scale: Severity: Absent, very mild, mild, moderate and severe, where the normality of severity is absent.Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time. | will be evaluated at the end of the treatment at the final visit (day 10) | 
| Foreign Body Sensation (FBS) | Foreign body sensation is a nominal variable that will be evaluated by direct questioning to the research subject, then it will be staged according to the following scale: Severity: Absent, very mild, mild, moderate and severe, where the normality of severity is absent. Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time. | will be evaluated at the end of the treatment at the final visit (day 10) | 
| Ocular Pruritus (P) | Ocular pruritus is a nominal variable that will be evaluated by direct questioning to the research subject, then it will be staged according to the following scale: Severity: Absent, very mild, mild, moderate and severe, where the normality of severity is absent. Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time. | will be evaluated at the end of the treatment at the final visit (day 10) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Humylub PF, artificial tears, Ophthalmic lubricant, Chondroitin sulfate, Sodium hyaluronate