Conjunctivitis, Conjunctivitis, Bacterial
Conditions
Keywords
ocular antibiotic, quinolone, levofloxacin, ophthalmic antibiotic, antibiotic in drops
Brief summary
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
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.
Interventions
DRUGPRO-174
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
DRUGSophixín Ofteno®
* 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
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The blinding will correspond to the research subject and the principal investigator. In addition, the statistical analysis will be carried out in a blinded manner for the partial and final analysis. The masking will be done using boxes in the primary packaging identical in the two groups. Blinding for the research subject and the researcher will be done by replacing the commercial labels in the case of the comparator in the bottles and the use of identical labels that contain the allocation number. Blinding may be opened in the following cases: 1. Presence of a serious adverse event. 2. Safety alarm due to the use of the drugs under study. 3. In case the sponsor determines it for any reason of security or other reason that considers pertinent.
Intervention model description
Phase I clinical trial, controlled, of parallel groups, double blind, randomized, exploratory.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events (EAS) | during the 12 days of evaluation, including the safety call (day 12). | 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. |
| Ocular Burning (OB) | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Eyes With Epithelial Defects (ED) by Grade | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
| Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
| Number of Eyes With Foreign Body Sensation (FBS) by Grade | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
| Intraocular Pressure (IOP) | will be evaluated at the end of the treatment at the final visit (day 7) | 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 |
| Number of Eyes of Chemosis | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
| Visual Capacity | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
| Number of Eyes With Ocular Pruritus (P) by Grade | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
| Breakup Time (BUT) | will be evaluated at the end of the treatment at the final visit (day 7) | 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. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-174 Active ingredient: Levofloxacin 0.5%
o Dosage: 1 drop in both eyes, 8 times a day during the waking period
PRO-174: 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 | 15 |
| Sophixín Ofteno® o Dosage: 1 drop in both eyes, 8 times a day during the waking period
Sophixín Ofteno®: o 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 | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | PRO-174 | Total | Sophixín Ofteno® |
|---|---|---|---|
| Age, Continuous | 23.67 years STANDARD_DEVIATION 4.15 | 26.3 years STANDARD_DEVIATION 6.77 | 28.93 years STANDARD_DEVIATION 9.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 30 Participants | 15 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Mexico | 15 Participants | 30 Participants | 15 Participants |
| Sex: Female, Male Female | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 11 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 9 / 15 | 8 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: during the 12 days of evaluation, including the safety call (day 12).
Population: the analysis of the population was by protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-174 | Number of Adverse Events (EAS) | 11 adverse events |
| Sophixín Ofteno® | Number of Adverse Events (EAS) | 10 adverse events |
p-value: 0.749Wilcoxon (Mann-Whitney)
Primary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: the analysis of the study population was by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-174 | Ocular Burning (OB) | Normal | 86.7 percentage of participants |
| PRO-174 | Ocular Burning (OB) | Very mild | 6.7 percentage of participants |
| PRO-174 | Ocular Burning (OB) | mild | 6.7 percentage of participants |
| Sophixín Ofteno® | Ocular Burning (OB) | Normal | 57.1 percentage of participants |
| Sophixín Ofteno® | Ocular Burning (OB) | Very mild | 14.3 percentage of participants |
| Sophixín Ofteno® | Ocular Burning (OB) | mild | 28.6 percentage of participants |
p-value: 0.041Chi-squared
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: The study population was analyzed by protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-174 | Breakup Time (BUT) | 15.27 seconds | Standard Deviation 2.7 |
| Sophixín Ofteno® | Breakup Time (BUT) | 15.79 seconds | Standard Deviation 2.9 |
p-value: 0.495Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: The study population was analyzed by protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-174 | Intraocular Pressure (IOP) | 12.53 mmHg | Standard Deviation 1 |
| Sophixín Ofteno® | Intraocular Pressure (IOP) | 12.68 mmHg | Standard Deviation 1.7 |
p-value: 0.694Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: the statistical analysis of the sample was performed by protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-174 | Number of Eyes of Chemosis | 0 eyes |
| Sophixín Ofteno® | Number of Eyes of Chemosis | 0 eyes |
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: The study population was analyzed by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-174 | Number of Eyes With Epithelial Defects (ED) by Grade | Green lissamine grade 1 | 2 eyes |
| PRO-174 | Number of Eyes With Epithelial Defects (ED) by Grade | Green lissamine grade 0 | 28 eyes |
| PRO-174 | Number of Eyes With Epithelial Defects (ED) by Grade | luorescein grade 1 | 3 eyes |
| PRO-174 | Number of Eyes With Epithelial Defects (ED) by Grade | fluorescein grade 0 | 27 eyes |
| Sophixín Ofteno® | Number of Eyes With Epithelial Defects (ED) by Grade | fluorescein grade 0 | 28 eyes |
| Sophixín Ofteno® | Number of Eyes With Epithelial Defects (ED) by Grade | Green lissamine grade 1 | 0 eyes |
| Sophixín Ofteno® | Number of Eyes With Epithelial Defects (ED) by Grade | luorescein grade 1 | 0 eyes |
| Sophixín Ofteno® | Number of Eyes With Epithelial Defects (ED) by Grade | Green lissamine grade 0 | 28 eyes |
p-value: 0.492Chi-squared
p-value: 0.238Chi-squared, Corrected
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: The study population was analyzed by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-174 | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Very mild | 0 eyes |
| PRO-174 | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Moderate | 0 eyes |
| PRO-174 | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Mild | 0 eyes |
| PRO-174 | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Severe | 0 eyes |
| PRO-174 | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Absent | 30 eyes |
| Sophixín Ofteno® | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Severe | 0 eyes |
| Sophixín Ofteno® | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Absent | 28 eyes |
| Sophixín Ofteno® | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Very mild | 0 eyes |
| Sophixín Ofteno® | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Mild | 0 eyes |
| Sophixín Ofteno® | Number of Eyes With Foreign Body Sensation (FBS) by Grade | Moderate | 0 eyes |
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: The study population was analyzed by protocol grade 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-174 | Number of Eyes With Ocular Pruritus (P) by Grade | Very mild | 4 number of eyes with Ocular pruritus |
| PRO-174 | Number of Eyes With Ocular Pruritus (P) by Grade | Moderate | 0 number of eyes with Ocular pruritus |
| PRO-174 | Number of Eyes With Ocular Pruritus (P) by Grade | Mild | 2 number of eyes with Ocular pruritus |
| PRO-174 | Number of Eyes With Ocular Pruritus (P) by Grade | Severe | 0 number of eyes with Ocular pruritus |
| PRO-174 | Number of Eyes With Ocular Pruritus (P) by Grade | Absent | 24 number of eyes with Ocular pruritus |
| Sophixín Ofteno® | Number of Eyes With Ocular Pruritus (P) by Grade | Severe | 0 number of eyes with Ocular pruritus |
| Sophixín Ofteno® | Number of Eyes With Ocular Pruritus (P) by Grade | Absent | 24 number of eyes with Ocular pruritus |
| Sophixín Ofteno® | Number of Eyes With Ocular Pruritus (P) by Grade | Very mild | 2 number of eyes with Ocular pruritus |
| Sophixín Ofteno® | Number of Eyes With Ocular Pruritus (P) by Grade | Mild | 2 number of eyes with Ocular pruritus |
| Sophixín Ofteno® | Number of Eyes With Ocular Pruritus (P) by Grade | Moderate | 0 number of eyes with Ocular pruritus |
p-value: 0.741Chi-squared, Corrected
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
Population: The study population was analyzed by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-174 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | very mild | 3.3 percentage of eyes |
| PRO-174 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | moderate | 0 percentage of eyes |
| PRO-174 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Mild | 0 percentage of eyes |
| PRO-174 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | severo | 0 percentage of eyes |
| PRO-174 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | normal | 96.7 percentage of eyes |
| Sophixín Ofteno® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | severo | 0 percentage of eyes |
| Sophixín Ofteno® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | normal | 92.9 percentage of eyes |
| Sophixín Ofteno® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | very mild | 0 percentage of eyes |
| Sophixín Ofteno® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Mild | 0 percentage of eyes |
| Sophixín Ofteno® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | moderate | 7.1 percentage of eyes |
p-value: 0.213Chi-squared
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-174 | Visual Capacity | 20.6 units on a scale (snellen) | Standard Deviation 2.17 |
| Sophixín Ofteno® | Visual Capacity | 20 units on a scale (snellen) | Standard Deviation 0 |
p-value: 0.11Wilcoxon (Mann-Whitney)