Safety and Tolerability of the Ophthalmic Gel PRO-165 Versus Artelac® Nightime Gel

Study Overview
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Brief Summary
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Objective: To assess the safety and tolerability of the PRO-165 formulation on the ocular surface of ophthalmologically and clinically healthy subjects. Hypothesis: Ophthalmic gel PRO-165 presents a safety and tolerability profile similar to Artelac® Nightime Gel in ophthalmological and clinically healthy subjects. Phase I clinical study, controlled, of parallel groups, double blind, randomized, exploratory Therapeutic indication of PRO-165: Eye lubricant

Detailed Description
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The study subjects will be recruited from various research centers in western and central Mexico. Each research center has a monitoring plan specified according to the recruitment capabilities of the same, which must be at least once a month, where the queries of your data entered into the electronic case report report will be reported to the center. (e-CRF) for which it has as time limit the next monitoring visit to make the pertinent changes. The report of adverse events will be made according to the standard operating procedure (PNO) where it specifies, according to Official Mexican Standard 220 (NOM 220), that the signs or symptoms of adverse events will be reported based on the Medical Dictionary. for Regulatory Activities, for which the sponsor has version 20.1 in Spanish. For serious adverse events (SAEs) will be reported in accordance with the standardized operation procedure of pharmacovigilance of the sponsor, which adheres to the guidelines of NOM 220 and international regulations, these will be reported in the regulatory framework to the regulatory entity within a period of time no more than 7 days. The study is registered in the National Registry of Clinical Trials (RNEC), entity equivalent to Clinical Trials in Mexico. The quality assurance plan is carried out by the sponsor through the Quality Assurance agent in Clinical Research, whose function is to conduct inspections and audits of the research sites to document and generate reports of deviations from the protocol. In addition to the visits of the monitoring plan, the reliability of the data is guaranteed. To verify the integrity, veracity and reliability of the data entered into the e-CRF, the monitors of each center will check the information uploaded to the portal with that reported in the source document of the principal investigator (PI), such as clinical notes, clinical history and documents. and formats attached to the research protocol, physical case report format, as well as those provided by the sponsor to the PI (subject's diary and quality and satisfaction survey). The e-CRF used for this clinical study is provided by an internationally certified provider with the highest quality standards, protection of information under current regulations and confidentiality guarantee. The information that the PIs enter into the e-CRF is collated and verified by the clinical monitors and by the service provider's personnel, later reviewed and approved by the medical ophthalmologist researcher and by the Clinical Security Pharmacologist, who authorize the monitored data of clinical information and safety of the study molecule, respectively.

Official Title
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Phase I Clinical Study, to Evaluate the Safety and Tolerability of the Ophthalmic Gel PRO-165 Versus Artelac® Nightime Gel, on the Ocular Surface of Ophthalmological and Clinically Healthy Subjects

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: PRO-165
* Drug: Artelac


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, three element blood chemistry 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: 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 lactating. Women without a history of bilateral tubal obstruction, 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. Known diagnosis of liver disease Inability to attend or answer the evaluations made in each of the visits. Positive tobacco use (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). Contact lens users. Medical and therapeutic exclusion criteria. 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 entry into 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: controlled, of parallel groups, double blind, randomized, exploratory
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-165<br>Dose: one drop of gel, 4 times a day during the waking period, in the bottom of the right eye sac | Drug: PRO-165<br>* PRO-165 Chondroitin sulfate 0.18% / sodium hyaluronate 0.2%, ophthalmic gel. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico.<br>* Other names: chondroitin sulfate 0.18%;|
| Active Comparator: 1. Artelac® Nightime Gel<br>Dose: one drop of gel, 4 times a day during the waking period, in the bottom of the right eye sac | Drug: Artelac<br>* Artelac® Nightime Gel. 0.2% Carbomer, ophthalmic gel. Made in Germany by: Dr. Gerhard Mann Chem Pharm. Imported and marketed by: Bausch & Lomb México, S.A. de C.V.<br>* Other names: Carbomer 0.2%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | The Principal Investigator will register the Events Adverse (EA) that the subjects of the study will present. The EAs will be expressed as absent or present and the number of cases will be counted by study group. | during the 13 days of evaluation, including the safety call (day 13). | 
| 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). Similar to the index for ocular surface diseases, the ocular comfort index (ICO) evaluates symptoms. The ICO contains 6 items that focus on the discomfort associated with the ocular surface. Each of these questions has two parts, which inquire separately the frequency and severity of the symptoms. The evaluator will deliver the questionnaire to the subject and allow the subject to answer it calmly without any pressure and / or coercion, will only assist him if he has difficulty understanding any of the questions. | day 11 at the final visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual ability (VA) | The VA will be evaluated basally, without refractive correction with the Snellen chart. Which will be located in a place with adequate lighting, natural or artificial and at a distance of 3 meters from the subject to be evaluated | day 11 at the final visit | 
| Intraocular pressure (IOP) | Tonometry is the objective measure of Intraocular pressure, based primarily on the force required to flatten the cornea, or the degree of corneal indentation produced by a fixed force. Goldman's tonometry is based on the Imbert-Fick principle. the result will be expressed in millimeters of mercury and the comparison between groups will be carried out. | day 11 at the final visit | 
| Symptomatology post instillation | The subject will be questioned if after applying the medication he felt burning, pruritus, a foreign body sensation and blurred vision. Presence or absence: it will be marked as present (1) or absent (0) for each of the symptoms questioned | day 11 at the final visit | 
| 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. | day 11 at the final visit | 
| 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. | day 11 at the final visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PRO-165, sodium hyaluronate, Chondroitin sulfate 0.18%