Bacterial Conjunctivitis
Conditions
Brief summary
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
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.
Interventions
DRUGPRO-157
PRO-157 (Pazufloxacin 0.06%) Laboratories Sophia S.A. de C.V., ophthalmic solution
DRUGVigamox
Vigamox® (Moxifloxacin 0.5%), Alcon Laboratories, S.A. de C.V., ophthalmic solution
DRUGZymar®
Zymar® (Gatifloxacin 0.3%), Allergan, S.A. de C.V., ophthalmic solution
DRUGLagricel Ofteno®
Lagricel Ofteno® Sodium hyaluronate 0.4%, Laboratories Sophia S.A. de C.V., ophthalmic solution
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Days to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Bacterial Culture | up to one week | 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. |
| Adverse Events | during the intervention period for 7 days, and 15 days after the final visit | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chemosis Frequency | up to one week | 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. |
| Cases Frequency of Ocular Secretion | Up to one week. | 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. |
| Frequency of Corneal Epithelial Defects | Up to one week | 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. |
| Eyelid Edema Frequency | Up to one week | 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. |
| Number of Cases of Conjunctival Hyperemia | up to one week | 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. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-157 BID One drop twice a day for 7 days (PRO-157=pazufloxacin 0.6%) | 27 |
| PRO-157 BID One drop twice a day for 7 days (PRO-157=pazufloxacin 0.6%) | 54 |
| PRO-157 TID One drop three times a day for 7 days (PRO-157=pazufloxacin 0.6%) | 19 |
| PRO-157 TID One drop three times a day for 7 days (PRO-157=pazufloxacin 0.6%) | 38 |
| PRO-157 QID One drop three times a day for 7 days (PRO-157=pazufloxacin 0.6%) | 24 |
| PRO-157 QID One drop three times a day for 7 days (PRO-157=pazufloxacin 0.6%) | 48 |
| Moxifloxacine One drop four times a day for 7 days Moxifloxacin 0.5% (Vigamox®). | 21 |
| Moxifloxacine One drop four times a day for 7 days Moxifloxacin 0.5% (Vigamox®). | 42 |
| Gatifloxacine One drop four times a day for 7 days Gatifloxacin 0.3% (Zymar®). | 20 |
| Gatifloxacine One drop four times a day for 7 days Gatifloxacin 0.3% (Zymar®). | 40 |
| Total | 333 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Did not receive intervention | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Excluded from analysis | 1 | 3 | 1 | 1 | 1 |
| Overall Study | Lack of Efficacy | 1 | 4 | 4 | 5 | 8 |
| Overall Study | Lost to Follow-up | 1 | 4 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | PRO-157 BID | PRO-157 TID | PRO-157 QID | Moxifloxacine | Gatifloxacine | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 3 Participants | 7 Participants | 5 Participants | 5 Participants | 27 Participants |
| Age, Categorical >=65 years | 9 Participants | 3 Participants | 7 Participants | 5 Participants | 7 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 13 Participants | 10 Participants | 11 Participants | 8 Participants | 53 Participants |
| Age, Continuous | 41.1 years STANDARD_DEVIATION 27.9 | 37.2 years STANDARD_DEVIATION 21.3 | 43.3 years STANDARD_DEVIATION 25.7 | 39.9 years STANDARD_DEVIATION 26.9 | 43.4 years STANDARD_DEVIATION 29.5 | 40.8 years STANDARD_DEVIATION 26.2 |
| Region of Enrollment Mexico Mexicans | 27 Participants | 19 Participants | 24 Participants | 21 Participants | 20 Participants | 111 Participants |
| Region of Enrollment Mexico others | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 10 Participants | 16 Participants | 13 Participants | 11 Participants | 69 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 8 Participants | 8 Participants | 9 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 30 | 5 / 30 | 7 / 30 | 3 / 30 | 6 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 | 1 / 30 | 1 / 30 |
Outcome results
Primary
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.
Time frame: during the intervention period for 7 days, and 15 days after the final visit
Population: Treatment analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-157 BID (2 Times Per Day) | Adverse Events | 7 events |
| PRO-157 TID (3 Times Per Day) | Adverse Events | 5 events |
| PRO-157 QID (4 Times Per Day) | Adverse Events | 7 events |
| Moxifloxacin (Vigamox®) | Adverse Events | 4 events |
| Gatifloxacin (Zymar®) | Adverse Events | 7 events |
p-value: 0.372Chi-squared, Corrected
Primary
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.
Time frame: up to one week
Population: Treatment analysis, a culture was performed per eye
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-157 BID (2 Times Per Day) | Change From Baseline Bacterial Culture | basal cultures positives | 30 cultures |
| PRO-157 BID (2 Times Per Day) | Change From Baseline Bacterial Culture | final cultures negatives | 17 cultures |
| PRO-157 TID (3 Times Per Day) | Change From Baseline Bacterial Culture | basal cultures positives | 16 cultures |
| PRO-157 TID (3 Times Per Day) | Change From Baseline Bacterial Culture | final cultures negatives | 14 cultures |
| PRO-157 QID (4 Times Per Day) | Change From Baseline Bacterial Culture | basal cultures positives | 26 cultures |
| PRO-157 QID (4 Times Per Day) | Change From Baseline Bacterial Culture | final cultures negatives | 16 cultures |
| Moxifloxacin (Vigamox®) | Change From Baseline Bacterial Culture | final cultures negatives | 28 cultures |
| Moxifloxacin (Vigamox®) | Change From Baseline Bacterial Culture | basal cultures positives | 29 cultures |
| Gatifloxacin (Zymar®) | Change From Baseline Bacterial Culture | basal cultures positives | 17 cultures |
| Gatifloxacin (Zymar®) | Change From Baseline Bacterial Culture | final cultures negatives | 15 cultures |
p-value: 0.002Chi-squared
Secondary
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.
Time frame: Up to one week.
Population: treatment analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-157 BID (2 Times Per Day) | Cases Frequency of Ocular Secretion | 0 secretion cases reported |
| PRO-157 TID (3 Times Per Day) | Cases Frequency of Ocular Secretion | 3 secretion cases reported |
| PRO-157 QID (4 Times Per Day) | Cases Frequency of Ocular Secretion | 0 secretion cases reported |
| Moxifloxacin (Vigamox®) | Cases Frequency of Ocular Secretion | 7 secretion cases reported |
| Gatifloxacin (Zymar®) | Cases Frequency of Ocular Secretion | 2 secretion cases reported |
p-value: 0.341Chi-squared, Corrected
Secondary
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.
Time frame: up to one week
Population: Treatment analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-157 BID (2 Times Per Day) | Chemosis Frequency | 0 chemosis cases reported |
| PRO-157 TID (3 Times Per Day) | Chemosis Frequency | 0 chemosis cases reported |
| PRO-157 QID (4 Times Per Day) | Chemosis Frequency | 0 chemosis cases reported |
| Moxifloxacin (Vigamox®) | Chemosis Frequency | 6 chemosis cases reported |
| Gatifloxacin (Zymar®) | Chemosis Frequency | 2 chemosis cases reported |
p-value: 0.003Chi-squared, Corrected
Secondary
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.
Time frame: Up to one week
Population: Treatment analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-157 BID (2 Times Per Day) | Eyelid Edema Frequency | 6 eyelid edema cases reported |
| PRO-157 TID (3 Times Per Day) | Eyelid Edema Frequency | 0 eyelid edema cases reported |
| PRO-157 QID (4 Times Per Day) | Eyelid Edema Frequency | 4 eyelid edema cases reported |
| Moxifloxacin (Vigamox®) | Eyelid Edema Frequency | 4 eyelid edema cases reported |
| Gatifloxacin (Zymar®) | Eyelid Edema Frequency | 6 eyelid edema cases reported |
p-value: 0.216Chi-squared, Corrected
Secondary
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.
Time frame: Up to one week
Population: Treatment analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-157 BID (2 Times Per Day) | Frequency of Corneal Epithelial Defects | 9 Corneal defects cases reported |
| PRO-157 TID (3 Times Per Day) | Frequency of Corneal Epithelial Defects | 4 Corneal defects cases reported |
| PRO-157 QID (4 Times Per Day) | Frequency of Corneal Epithelial Defects | 6 Corneal defects cases reported |
| Moxifloxacin (Vigamox®) | Frequency of Corneal Epithelial Defects | 5 Corneal defects cases reported |
| Gatifloxacin (Zymar®) | Frequency of Corneal Epithelial Defects | 5 Corneal defects cases reported |
p-value: 0.829Chi-squared, Corrected
Secondary
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.
Time frame: up to one week
Population: Treatment analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-157 BID (2 Times Per Day) | Number of Cases of Conjunctival Hyperemia | 17 hyperemia cases reported |
| PRO-157 TID (3 Times Per Day) | Number of Cases of Conjunctival Hyperemia | 1 hyperemia cases reported |
| PRO-157 QID (4 Times Per Day) | Number of Cases of Conjunctival Hyperemia | 5 hyperemia cases reported |
| Moxifloxacin (Vigamox®) | Number of Cases of Conjunctival Hyperemia | 7 hyperemia cases reported |
| Gatifloxacin (Zymar®) | Number of Cases of Conjunctival Hyperemia | 8 hyperemia cases reported |
p-value: 0.001Chi-squared, Corrected