Dry Eye, Dry Eye Syndrome of Unspecified Lacrimal Gland
Conditions
Keywords
dry eye, eye lubricants, eye lubricant gel, PRO-167
Brief summary
Title of the study: Phase I clinical trial, to evaluate the safety and tolerability of the ophthalmic gel PRO-167 versus Corneregel®, on the ocular surface of ophthalmological and clinically healthy subjects. Methodology: Phase I clinical trial, controlled, of parallel groups, double blind, randomized, exploratory. Goals: To evaluate the safety and tolerability of the ophthalmic gel PRO-167 manufactured by Laboratorios Sophia S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis: Ophthalmic gel PRO-167 has a safety and tolerability profile similar to that of its comparator in healthy subjects.
Detailed description
Therapeutic indication: Corneal surface reepithelizing 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 quantitative variables. The difference between the qualitative variables will be analyzed by means of square chi (Chi2). An alpha ≤ 0.05 will be considered significant. Study period: 3 to 4 months Development phase: I Number of patients: 24 subjects, divided into 2 groups (12 eyes exposed per group) Test product, dose and route of administration, lot number: PRO-167. Dexpanthenol 5%. Ophthalmic gel produced by Laboratorios Sophia, S.A. de C.V., Zapopan, Jalisco, Mexico. * Dose: a strip approximately 1 cm long, 4 times a day during the period of vigil, in the bottom of the right eye sac. * Route of administration: ophthalmic. Reference product, dose and route of administration, lot: * Corneregel. Dexpanthenol 5%. Ophthalmic gel developed by Bausch and Lomb, Berlin, Germany. * Dose: a strip approximately 1 cm long, 4 times a day during the period of vigil, in the bottom of the right eye sac. * Route of administration: ophthalmic Evaluation criteria: Primary security outcome variable: \- Density of goblet cells. Secondary security variables: * Epithelial defects in cornea and conjunctiva. * Presence of adverse events. Secondary outcome variables: * Intraocular pressure. * Visual ability * Break time of the tear film. Outcome variables of tolerability: * Burning. * Foreign body sensation. * Itching. * Eye comfort index.
Interventions
DRUGPRO-167
Dexpanthenol 5%. Ophthalmic gel produced by Laboratorios Sophia, S.A. of C.V., Zapopan, Jalisco, Mexico. Route of administration: ophthalmic
DRUGCorneregel
Dexpanthenol 5%. Ophthalmic gel developed by Bausch and Lomb, Berlin, Germany. Route of administration: ophthalmic
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. * 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 breastfeeding. * Women without a history of hysterectomy, oophorectomy, 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. * Diagnosis of liver disease or triple 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Goblet Cell Density (GCD) | will be evaluated at the end of the treatment at the final visit (day 11) | the cells will be measured per square millimeter, it is a continuous variable taken by means of cytology per impression, the normal value is higher than 500 cells per square millimeter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure (IOP) | will be evaluated at the end of the treatment at the final visit (day 11) | 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 |
| Breakup Time (BUT) | will be evaluated at the end of the treatment at the final visit (day 11) | 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 greater than 10 seconds. |
| Chemosis | will be evaluated at the end of the treatment at the final visit (day 11) | 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. |
| Ocular Burning (OB) | will be evaluated at the end of the treatment at the final visit (day 11) | 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.Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time. |
| Presence of Adverse Events (EAS) | during the 11 days of evaluation, including the safety call (day 13). | the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent. |
| Conjunctival Hyperemia (CH) | will be evaluated at the end of the treatment at the final visit (day 11) | 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. |
| Foreign Body Sensation (FBS) | will be evaluated at the end of the treatment at the final visit (day 11) | 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. Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time. |
| Ocular Pruritus (P) | will be evaluated at the end of the treatment at the final visit (day 11) | 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. Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time. |
| Epithelial Defects (ED) | will be evaluated at the end of the treatment at the final visit (day 11) | The epithelial defects will be evaluated by means of two stains, green lissamine, 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. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-167 Dose: a strip approximately 1 cm long, 4 times a day during the period of vigil, in the bottom
PRO-167: Dexpanthenol 5%. Ophthalmic gel produced by Laboratorios Sophia, S.A. of C.V., Zapopan, Jalisco, Mexico.
Route of administration: ophthalmic | 12 |
| PRO-167 Dose: a strip approximately 1 cm long, 4 times a day during the period of vigil, in the bottom
PRO-167: Dexpanthenol 5%. Ophthalmic gel produced by Laboratorios Sophia, S.A. of C.V., Zapopan, Jalisco, Mexico.
Route of administration: ophthalmic | 24 |
| Corneregel® Dose: a strip approximately 1 cm long, 4 times a day during the period of vigil, in the bottom of the right eye sac.
Corneregel: Dexpanthenol 5%. Ophthalmic gel developed by Bausch and Lomb, Berlin, Germany.
Route of administration: ophthalmic | 12 |
| Corneregel® Dose: a strip approximately 1 cm long, 4 times a day during the period of vigil, in the bottom of the right eye sac.
Corneregel: Dexpanthenol 5%. Ophthalmic gel developed by Bausch and Lomb, Berlin, Germany.
Route of administration: ophthalmic | 24 |
| Total | 72 |
Baseline characteristics
| Characteristic | PRO-167 | Total | Corneregel® |
|---|---|---|---|
| Age, Continuous | 29.25 years STANDARD_DEVIATION 6.84 | 28.71 years STANDARD_DEVIATION 5.9 | 28.17 years STANDARD_DEVIATION 4.95 |
| 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 24 Participants | 12 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Mexico | 12 participants | 24 participants | 12 participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 7 / 12 | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Goblet Cell Density (GCD)
the cells will be measured per square millimeter, it is a continuous variable taken by means of cytology per impression, the normal value is higher than 500 cells per square millimeter
Time frame: will be evaluated at the end of the treatment at the final visit (day 11)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-167 | Goblet Cell Density (GCD) | 444 cells/mm^2 | Standard Deviation 112.5 |
| Corneregel® | Goblet Cell Density (GCD) | 440 cells/mm^2 | Standard Deviation 127.2 |
p-value: 0.285Wilcoxon (Mann-Whitney)
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 greater than 10 seconds.
Time frame: will be evaluated at the end of the treatment at the final visit (day 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-167 | Breakup Time (BUT) | 8.92 seconds | Standard Deviation 2.1 |
| Corneregel® | Breakup Time (BUT) | 7.75 seconds | Standard Deviation 2.1 |
p-value: 0.137Wilcoxon (Mann-Whitney)
Secondary
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 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-167 | Chemosis | 0 cases |
| Corneregel® | Chemosis | 0 cases |
Secondary
Conjunctival Hyperemia (CH)
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 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-167 | Conjunctival Hyperemia (CH) | Normal | 16.7 percentage of participants |
| PRO-167 | Conjunctival Hyperemia (CH) | Very mild | 66.6 percentage of participants |
| PRO-167 | Conjunctival Hyperemia (CH) | Mild | 16.7 percentage of participants |
| Corneregel® | Conjunctival Hyperemia (CH) | Very mild | 66.7 percentage of participants |
| Corneregel® | Conjunctival Hyperemia (CH) | Normal | 8.3 percentage of participants |
| Corneregel® | Conjunctival Hyperemia (CH) | Mild | 25 percentage of participants |
p-value: 1Chi-squared
Secondary
Epithelial Defects (ED)
The epithelial defects will be evaluated by means of two stains, green lissamine, 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 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-167 | Epithelial Defects (ED) | grade II | 0 cases |
| PRO-167 | Epithelial Defects (ED) | grade 0 | 8 cases |
| PRO-167 | Epithelial Defects (ED) | grade I | 4 cases |
| Corneregel® | Epithelial Defects (ED) | grade I | 3 cases |
| Corneregel® | Epithelial Defects (ED) | grade 0 | 8 cases |
| Corneregel® | Epithelial Defects (ED) | grade II | 1 cases |
p-value: 0.561Chi-squared, Corrected
Secondary
Foreign Body Sensation (FBS)
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. Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time.
Time frame: will be evaluated at the end of the treatment at the final visit (day 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-167 | Foreign Body Sensation (FBS) | Absent | 79.2 percentage of participants |
| PRO-167 | Foreign Body Sensation (FBS) | Very mild | 20.8 percentage of participants |
| PRO-167 | Foreign Body Sensation (FBS) | Mild | 0 percentage of participants |
| PRO-167 | Foreign Body Sensation (FBS) | Moderate | 0 percentage of participants |
| Corneregel® | Foreign Body Sensation (FBS) | Moderate | 0 percentage of participants |
| Corneregel® | Foreign Body Sensation (FBS) | Absent | 91.7 percentage of participants |
| Corneregel® | Foreign Body Sensation (FBS) | Mild | 0 percentage of participants |
| Corneregel® | Foreign Body Sensation (FBS) | Very mild | 8.3 percentage of participants |
p-value: 0.317Chi-squared, Corrected
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 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-167 | Intraocular Pressure (IOP) | 13.14 mmHg | Standard Deviation 2.22 |
| Corneregel® | Intraocular Pressure (IOP) | 13.56 mmHg | Standard Deviation 1.99 |
p-value: 0.839Wilcoxon (Mann-Whitney)
Secondary
Ocular Burning (OB)
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.Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time.
Time frame: will be evaluated at the end of the treatment at the final visit (day 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-167 | Ocular Burning (OB) | moderate | 4.2 percentage of participants |
| PRO-167 | Ocular Burning (OB) | Absent | 66.7 percentage of participants |
| PRO-167 | Ocular Burning (OB) | Severe | 0 percentage of participants |
| PRO-167 | Ocular Burning (OB) | mild | 29.2 percentage of participants |
| Corneregel® | Ocular Burning (OB) | Severe | 0 percentage of participants |
| Corneregel® | Ocular Burning (OB) | moderate | 8.3 percentage of participants |
| Corneregel® | Ocular Burning (OB) | mild | 16 percentage of participants |
| Corneregel® | Ocular Burning (OB) | Absent | 75 percentage of participants |
p-value: 0.667Chi-squared, Corrected
Secondary
Ocular Pruritus (P)
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. Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time.
Time frame: will be evaluated at the end of the treatment at the final visit (day 11)
Population: the statistical analysis of the sample was carried out by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-167 | Ocular Pruritus (P) | Moderate | 0 percentage of participants |
| PRO-167 | Ocular Pruritus (P) | Absent | 41.7 percentage of participants |
| PRO-167 | Ocular Pruritus (P) | Very mild | 50 percentage of participants |
| PRO-167 | Ocular Pruritus (P) | Mild | 8.3 percentage of participants |
| Corneregel® | Ocular Pruritus (P) | Mild | 16.7 percentage of participants |
| Corneregel® | Ocular Pruritus (P) | Moderate | 0 percentage of participants |
| Corneregel® | Ocular Pruritus (P) | Very mild | 16.7 percentage of participants |
| Corneregel® | Ocular Pruritus (P) | Absent | 66.7 percentage of participants |
p-value: 0.414Chi-squared, Corrected
Secondary
Presence of Adverse Events (EAS)
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 11 days of evaluation, including the safety call (day 13).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-167 | Presence of Adverse Events (EAS) | 7 cases |
| Corneregel® | Presence of Adverse Events (EAS) | 6 cases |
p-value: 0.68Wilcoxon (Mann-Whitney)