Safety and Efficacy of PRO-157 vs Moxifloxacin vs Gatifloxacin in Patients With Bacterial Conjunctivitis (Pazufloxacin)

Study Overview
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Brief Summary
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A randomized, double blind, phase II multicenter trial with the objective of assess the safety and efficacy of the PRO-157 ophthalmic solution in three different dosing regimens, versus Moxifloxacin, versus Gatifloxacin in patients with bacterial conjunctivitis. Number of participants: 300 eyes, 60 per group. Criteria for evaluation: Measurements of effectiveness: Main efficacy criterion It will be determined as effective if there is a reduction in number or species of bacterial flora by comparing the basal culture against the final culture among the five different patient groups. Reduction or absence of infection with the clinical evaluation through signs and symptoms. Safety Measurements: it will be determined by visual acuity and adverse events Patients recruited will be treated for 7, for protocol purpose, the infected eye (s) will be taken into account at the time of baseline, however the study medication and procedures will be applied and performed in both eyes to protect the healthy eye. The study is divided into the following evaluation periods: Visit 1 baseline (day 1), visit 2 (day 3), final visit (day 8) and a telephone call (day 23) for the evaluation of adverse events. Subjects will be allocated to any of the following regimen dosages: PRO-157 1 drop 2 times daily PRO-157 1 drop 3 times daily PRO-157 1 drop 4 times daily Moxifloxacin 1 drop 3 times daily Gatifloxacin 1 drop 3 times daily. All regimen dosage will have a duration of 7 days. An artificial tear preservative free (Lagricel Ofteno®) will also be applied 15 minutes before instillation of study drug, during study period. Data Analysis: The data will be analyzed by Intention to Treat (ITT) and per Protocol (PP) in which each of the variables is described, the ITT population will be constituted by all subjects recruited who have received at least one dose of the study, the PP population will be the subset of ITT composed of all subjects without any major deviation from the protocol and the bivariate analysis will be performed in this group. Continuous quantitative variables are expressed and presented by measures of central tendency and dispersion (mean, standard deviation and ranges). Qualitative nominal and ordinal variables are presented by means of frequencies and proportions. The level of significance was an alpha of 0.05 or less.

Detailed Description
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Lagricel Ofteno® is a registered trademark, therefore the use of the same throughout the document can not be translated into the English language. PRO-157, the acronym is part of an internal code used to record formulations or research projects and the numbers indicate consecutive of the molecule under study.

Official Title
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A Randomized, Double Blind, Phase II Multicenter Trial to Evaluate the Safety and Efficacy of PRO-157 Ophthalmic Solution in Three Different Dosing Regimen Versus Moxifloxacin Versus Gatifloxacin in Patients With Bacterial Conjunctivitis.

Conditions
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Bacterial Conjunctivitis

Intervention / Treatment
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* Drug: PRO-157
* Drug: Vigamox
* Drug: Zymar®
* Drug: Lagricel Ofteno®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obtained from physician office visit. Diagnosis of bacterial conjunctivitis (signs and / or symptoms and / or culture). Informed Consent signed and dated (consent of the parents for minor patients). Exclusion Criteria: absence of written informed consent. Women of childbearing age, without contraceptive use (oral contraceptive pill, contraceptive intrauterine device, contraceptive implant, patch or condom). Pregnant or breastfeeding women. Subjects that could not be evaluated partially or totally according to the protocol. Subjects with topical, systemic or intravenous medication with any type of antibiotic on the day of the baseline visit. Subjects with topical, systemic or intravenous medication with any type of medication that interferes decisively with the results of the study. Subjects with a hypersensitivity history to any component or analogues of the formulation product. Positive drug addiction (smoking, alcoholism, marijuana). Subjects with a history of participation in any clinical study in the last 40 days prior to their evaluation. incapacity to give informed consent owing to mental disorder or legal condition. Any major anomaly detected during the clinical examination, tests that could interfere with the performance of the study or with the efficacy and safety evaluations.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-157 BID (2 times per day)<br>60 eyes of 30 research subjects will be evaluated with the following therapeutic regimen: instill one drop in each eye of PRO-157 (pazufloxacin), every 12 hours per day (BID), for 7 days instill one drop in each eye of Lagricel Ofteno® (Sodium hyaluronate 0.4%)every 6 hours per day, for 7 days. (Can be applied 15 minutes after PRO 157) | Drug: PRO-157<br>* PRO-157 (Pazufloxacin 0.06%) Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Pazufloxacin 0.06%, ophthalmic solution;Drug: Lagricel Ofteno®<br>* Lagricel Ofteno® Sodium hyaluronate 0.4%, Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Sodium hyaluronate 0.4%;|
| Experimental: PRO-157 TID (3 times per day)<br>60 eyes of 30 research subjects will be evaluated with the following therapeutic regimen: instill one drop in each eye of PRO-157 (pazufloxacin), every 8 hours per day (TID), for 7 days 15 minutes after, instill one drop in each eye of Lagricel Ofteno® (Sodium hyaluronate 0.4%) every 6 hours per day, for 7 days. (Can be applied 15 minutes after PRO 157) | Drug: PRO-157<br>* PRO-157 (Pazufloxacin 0.06%) Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Pazufloxacin 0.06%, ophthalmic solution;Drug: Lagricel Ofteno®<br>* Lagricel Ofteno® Sodium hyaluronate 0.4%, Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Sodium hyaluronate 0.4%;|
| Experimental: PRO-157 QID (4 times per day)<br>60 eyes of 30 research subjects will be evaluated with the following therapeutic regimen: instill one drop in each eye of PRO-157 (pazufloxacin), every 6 hours per day (QID), for 7 days 15 minutes after, instill one drop in each eye of Lagricel Ofteno® (Sodium hyaluronate 0.4%) every 6 hours per day, for 7 days. (Can be applied 15 minutes after PRO 157) | Drug: PRO-157<br>* PRO-157 (Pazufloxacin 0.06%) Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Pazufloxacin 0.06%, ophthalmic solution;Drug: Lagricel Ofteno®<br>* Lagricel Ofteno® Sodium hyaluronate 0.4%, Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Sodium hyaluronate 0.4%;|
| Active Comparator: Moxifloxacin (Vigamox®)<br>60 eyes of 30 research subjects will be evaluated with the following therapeutic regimen: instill one drop in each eye of Moxifloxacin, every 8 hours per day, for 7 days. 15 minutes after, instill one drop in each eye of Lagricel Ofteno® (Sodium hyaluronate 0.4%) every 6 hours per day for 7 days. (Can be applied 15 minutes after moxifloxacin) | Drug: Vigamox<br>* Vigamox® (Moxifloxacin 0.5%), Alcon Laboratories, S.A. de C.V., ophthalmic solution<br>* Other names: Moxifloxacin;Drug: Lagricel Ofteno®<br>* Lagricel Ofteno® Sodium hyaluronate 0.4%, Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Sodium hyaluronate 0.4%;|
| Active Comparator: Gatifloxacin (Zymar®)<br>60 eyes of 30 research subjects will be evaluated with the following therapeutic regimen: instill one drop in each eye of Gatifloxacin, every 8 hours per day, for 7 days. 15 minutes after, instill one drop in each eye of Lagricel Ofteno® (Sodium hyaluronate 0.4%) every 6 hours per day for 7 days.one drop 4 times a day for 7 days in each eye.(Can be applied 15 minutes after gatifloxacin) | Drug: Zymar®<br>* Zymar® (Gatifloxacin 0.3%), Allergan, S.A. de C.V., ophthalmic solution<br>* Other names: Gatifloxacin;Drug: Lagricel Ofteno®<br>* Lagricel Ofteno® Sodium hyaluronate 0.4%, Laboratories Sophia S.A. de C.V., ophthalmic solution<br>* Other names: Sodium hyaluronate 0.4%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Bacterial Culture | Efficacy will be determined comparing the cultures of the lower conjunctival pouch, of the baseline (day 1) against final visit (day 8), quantifying and identifying the colony forming units (CFU) by genus and species. The evaluated variable is discrete quantitative type and the scale of measurement used will be CFU x mL considering the eradication, reduction or proliferation of the bacterial agent. It will be determined as effective if there is a reduction in number of bacterial flora in at least 95% of the evaluated subjects. | up to one week | 
| Adverse Events | Number of adverse events: dependent variable, discrete quantitative, the number of adverse events per group will be compared at the end of the study and it will be considered safe if there is not greater increase of 5% of serious adverse events. | during the intervention period for 7 days, and 15 days after the final visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cases Frequency of Ocular Secretion | Secretion ocular: qualitative ordinal variable. The secretion was evaluated by subject of study as present / absent, taking into consideration that each study subject represents two probable cases, one for each eye. On this premise, the statistical analysis of the number of cases reported in the final visit was made by study group. | Up to one week. | 
| Number of Cases of Conjunctival Hyperemia | Conjunctival hyperemia: qualitative ordinal variable. The conjunctival hyperemia was evaluated by subject of study as present / absent, taking into consideration that each study subject represents two probable cases, one for each eye. On this premise, the statistical analysis of the number of cases reported in the final visit was made by study group. | up to one week | 
| Chemosis Frequency | Chemosis: qualitative ordinal variable, measurement scale absent or present. The chemosis was evaluated by subject of study as present / absent, taking into consideration that each study subject represents two probable cases, one for each eye. On this premise, the statistical analysis of the number of cases reported in the final visit was made by study group. | up to one week | 
| Eyelid Edema Frequency | Eyelid edema: qualitative ordinal variable, measurement scale absent or present.Between baseline (day 0) versus final visit (day 7). The eyelid edema was evaluated by subject of study as present / absent, taking into consideration that each study subject represents two probable cases, one for each eye. On this premise, the statistical analysis of the number of cases reported in the final visit was made by study group. | Up to one week | 
| Frequency of Corneal Epithelial Defects | Corneal epithelial defects: qualitative ordinal variable, measurement scale present or absent. The corneal epithelial defects was evaluated by subject of study as present / absent, taking into consideration that each study subject represents two probable cases, one for each eye. On this premise, the statistical analysis of the number of cases reported in the final visit was made by study group. | Up to one week |