Safety and Tolerability of the PRO-174 Versus Sophixín Ofteno®, on the Ocular Surface of Healthy Subjects

Study Overview
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Brief Summary
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Phase I clinical trial, to evaluate the safety and tolerability of the ophthalmic solution PRO-174 versus Sophixín Ofteno®, elaborated by Laboratorios Sophia, S.A. of C.V. on the ocular surface of ophthalmologically and clinically healthy subjects. Goals: To evaluate the safety and tolerability of the formulation PRO-174 manufactured by Laboratorios Sophia, S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis: The ophthalmic solution PRO-174 presents a safety and tolerability profile similar to the comparator in healthy subjects.

Detailed Description
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Phase I clinical trial, to evaluate the safety and tolerability of the ophthalmic solution PRO-174 versus Sophixín Ofteno®, elaborated by Laboratorios Sophia, S.A. of C.V. on the ocular surface of ophthalmologically and clinically healthy subjects. Goals: Methodology: Phase I clinical trial, controlled, of parallel groups, double blind, randomized, exploratory. Number of patients: 30 subjects, divided into 2 groups [15 subjects (30 eyes) exposed per group] Test product, dose and route of administration, lot number: PRO-174. Levofloxacin 0.5% ophthalmic solution. Prepared by Laboratorios Sophia, S.A. of C.V., Zapopan, Jalisco, Mexico. Dosage: 1 drop every 2 hours during the waking period (8 daily applications), on day 1 and 2; continuing with 1 drop every 4 hours during the waking period (4 daily applications) from day 3 to 7. Both eyes. Route of administration: ophthalmic Duration of treatment: 7 days 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 Mann-Whitney U test for the quantitative variables for the difference between the groups. The intra-group difference will be made with the Wilcoxon rank test. 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 Trial, to Evaluate the Safety and Tolerability of the Ophthalmic Solution PRO-174 Versus Sophixín Ofteno®, Elaborated by Laboratorios Sophia on the Ocular Surface of Ophthalmological and Clinically Healthy Subjects

Conditions
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Conjunctivitis, Conjunctivitis, Bacterial

Intervention / Treatment
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* Drug: PRO-174
* Drug: Sophixín Ofteno®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Systemically and ophthalmologically healthy subjects evaluated during the clinical history. Age between 18 to 45 years. Both genders. Blood tests (complete blood count, blood chemistry of three elements and liver function tests) within normal parameters specified by the reference laboratory with a lower and upper margin of 10%. Vital signs within normal parameters. (Vital signs at rest: blood pressure ≤ 139/89 mmHg, heart rate 60 -100 beats per minute and respiratory rate of 12-24 breaths per minute). Visual capacity 20/30 or better, in both eyes. Intraocular pressure ≥11 and ≤ 21 mmHg. Exclusion Criteria: General 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. Pregnant or lactating women. Women of childbearing age, who do not ensure a hormonal contraceptive method or intrauterine device during the study period or without a history of bilateral tubal obstruction, oophorectomy or hysterectomy; as fertile age we understand women who have not had their menopause, defined as 12 months since the last menstruation in women over 40 years. Subjects with participation in clinical research studies 90 days prior to inclusion in the present study. Diagnosis of liver disease or elevation to three times 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 amount and frequency) Positive alcoholism (specified as the consumption of alcoholic beverages, regardless of quantity and frequency, during the study intervention period). Contact lens users. An occlusive iridocorneal angle, defined as a trabecular mesh visible at less than 90 ° from the angular circumference to gonioscopy.

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, of parallel groups, double blind, randomized, exploratory.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-174<br>Active ingredient: Levofloxacin 0.5% o Dosage: 1 drop in both eyes, 8 times a day during the waking period | Drug: PRO-174<br>* Pharmaceutical form: ophthalmic solution Prepared by: Laboratorios Sophia, S.A. of C.V. Description of the solution: transparent solution, free of visible particles. Description of container: sterile multi-dose bottle<br>* Other names: Levofloxacin Ophthalmic Solution;|
| Active Comparator: Sophixín Ofteno®<br>o Dosage: 1 drop in both eyes, 8 times a day during the waking period | Drug: Sophixín Ofteno®<br>* Active substance: Ciprofloxacin 0.3% Pharmaceutical form: Ophthalmic solution Prepared by: Laboratorios Sophia, S.A. of C.V. Description of the solution: transparent solution, free of visible particles. Description of container: sterile multi-dose bottle<br>* Other names: Ciprofloxacin Ophthalmic solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events (EAS) | 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. | during the 12 days of evaluation, including the safety call (day 12). | 
| Ocular Burning (OB) | primary tolerability variable 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. | will be evaluated at the end of the treatment at the final visit (day 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 7) | 
| 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 7) | 
| Number of Eyes With Epithelial Defects (ED) by Grade | 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 7) | 
| 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 7) | 
| Number of Eyes With Foreign Body Sensation (FBS) by Grade | 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. | will be evaluated at the end of the treatment at the final visit (day 7) | 
| Number of Eyes With Ocular Pruritus (P) by Grade | 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. | will be evaluated at the end of the treatment at the final visit (day 7) | 
| 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 7) | 
| Visual Capacity | 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 higher scores indicate worse visual acuity. Snellen Scale: 20/200, 20/100, 20/70, 20/50, 20/40, 20/30, 20/25, 20/20, 20/15, 20/12, 20/10 only the denominator of the fraction of each case is reported and averaged per group. | will be evaluated at the end of the treatment at the final visit (day 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ocular antibiotic, quinolone, levofloxacin, ophthalmic antibiotic, antibiotic in drops