Glaucoma
Conditions
Keywords
Glaucoma, Krytantek, Krytantek PF, PRO-122
Brief summary
Therapeutic indication: Ocular hypotensive Use: Primary open-angle glaucoma and ocular hypertension. Objectives: To evaluate the safety and tolerability of the preservative-free formulation PRO-122 manufactured by Sophia Laboratories, S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis: The ophthalmic solution PRO-122 presents a profile of safety and tolerability similar to Krytantek Ofteno®, in healthy subjects. Methodology: Phase I clinical trial, controlled, parallel group, double blind, randomized. Number of patients: n=24 12 subjects per group (both eyes). Main inclusion criteria:Clinically healthy subjects.
Detailed description
Number of patients: n = 24 12 subjects per group (both eyes). Main inclusion criteria: Clinically healthy subjects. Treatment duration: 7 days. Duration of subject in the study: 15 to 22 days. Adverse events will be reported and cataloged based on the MedDRA dictionary and will be reported to the corresponding regulatory entity. The sponsor will carry out monitoring or quality visits to the research sites where it corroborates the information of the source documents and will contrast them with the information presented in the electronic CRF. Electronic case report forms will be evaluated by the clinical research associate and the clinical team of the sponsor (medical ophthalmologist researcher and pharmacologist of clinical safety). 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 by means of the Mann-Whitney U test for the quantitative variables for the difference between the groups. The difference between the qualitative variables will be analyzed by means of X2 (Chi2). An alpha ≤ 0.05 will be considered significant.
Interventions
DRUGPRO-122
* PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. * Route of administration: topical ophthalmic.
* \- 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. * \- Route of administration: topical ophthalmic.
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Blinding will correspond to the principal investigator and coinvestigator. In addition, the statistical analysis will be carried out in a blinded manner for the final analysis. Blinding can not be guaranteed in the subject. The masking will be done through the secondary container. The primary packaging will not be masked by the morphological difference between them. The sponsor and the research center will have two blind / non-blind teams. They will be identified by means of identical labels. Which, in accordance with current and applicable regulations, must contain at least: * Name, address and telephone number of the sponsor. * Pharmaceutical form and route of administration. * Lot Number. * Caption Exclusively for clinical studies * Date of Expiry
Intervention model description
Phase I clinical trial, controlled, parallel group, double blind, randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* \- Clinically healthy * Ability to give your signed informed consent, and show willingness to comply with study procedures and to modify your lifestyle activities (Section 6.2.2) * Age between 18 to 45 years. * Indistinct sex. * Women must ensure a hormonal contraceptive method or intrauterine device during the study period. * Blood tests: within normal parameters or with a range of ± 20% as long as the subject is clinically healthy. * Blood count (BH): Hemoglobin, erythrocytes, hematocrit, total leukocytes, platelets, mean corpuscular volume and mean corpuscular hemoglobin. * Blood chemistry of three elements (QS): Glucose, urea and creatinine. * Liver function tests (PFH): Aspartate Aminotransferase and Alanine Aminotransferase, total bilirubin, direct and indirect. * Visual ability 20/30 or better in both eyes. * Vital signs within normal parameters. * Intraocular pressure ≥10 and ≤ 21 mmHg.
Exclusion criteria
* Users of topical ophthalmic products of any kind. * Users of medicines, or herbal products, by any other route of administration, with the exception of hormonal contraceptives in the case of women. * Women who are pregnant or breastfeeding. * Participation in clinical research studies 90 days prior to inclusion in the present study. * Previous participation in this same study. * Users of contact lenses. * 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 admission to the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Eye Comfort Index | will be evaluated at the end of the treatment, at the final visit (day 8) | 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).The Eye comfort index contains items that focus on the discomfort associated with alterations of the ocular surface. Values closer or equal to one hundred (100) correspond to greater discomfort, while values closer or equal to zero (0) correspond to greater comfort. |
| Number of Adverse Events | during the 14 days of evaluation, including the safety call (day 14) | 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. it will be evaluated by the number of reported cases per group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Ability | will be evaluated at the end of the treatment, at the final visit (day 8) | 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 or 1.0 in decimal and the worst 20/200 or 0.1 in decimal number. For the appropriate management of the data, the result of the fraction obtained from the snellen scale is transformed to decimals, in this case subjects close to or equal to 1.0 have better visual acuity while subjects close to or equal to 0.1 have worse visual acuity. The decimal equivalence scale is the result of the division of the fraction obtained in the Snellen chart. where 20/20 = 1.0; Do not confuse with Logmar scale where 20/20 = 0.0 Equivalences Snellen Scale = decimals: 20/200=0.1, 20/100=0.2, 20/50=0.4, 20/40=0.5, 20/30=0.66, 20/25=0.8, 20/20=1.0, etc. |
| Participants With Chemosis | will be evaluated at the end of the treatment, at the final visit (day 8) | 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. |
| Participants With Conjunctival Hyperemia (CH) by Grade | will be evaluated at the end of the treatment, at the final visit (day 8) | 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 Epithelial Defects by Grade | will be evaluated at the end of the treatment, at the final visit (day 8) | The epithelial defects will be evaluated by means of two stains, green lissamine 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Intraocular Pressure | will be evaluated at the end of the treatment, at the final visit (day 8) | 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 |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-122 \- Dosage: 1 drop every 12 hours, in both eyes
PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico.
\- Route of administration: topical ophthalmic. | 12 |
| Krytantek Ofteno® \- Dosage: 1 drop every 12 hours, in both eyes
Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico.
\- - Route of administration: topical ophthalmic. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Krytantek Ofteno® | Total | PRO-122 |
|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 6.8 | 26.3 years STANDARD_DEVIATION 5.3 | 25.1 years STANDARD_DEVIATION 4.8 |
| Race/Ethnicity, Customized Latin | 12 Participants | 24 Participants | 12 Participants |
| Region of Enrollment Mexico | 12 Participants | 24 Participants | 12 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 13 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 | 11 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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).The Eye comfort index contains items that focus on the discomfort associated with alterations of the ocular surface. Values closer or equal to one hundred (100) correspond to greater discomfort, while values closer or equal to zero (0) correspond to greater comfort.
Time frame: will be evaluated at the end of the treatment, at the final visit (day 8)
Population: Analysis per protocol (PP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-122 | Eye Comfort Index | 24.6 units on a scale | Standard Deviation 12.6 |
| Krytantek Ofteno® | Eye Comfort Index | 27.0 units on a scale | Standard Deviation 12.8 |
p-value: 0.622Wilcoxon (Mann-Whitney)
Primary
Number of Adverse Events
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. it will be evaluated by the number of reported cases per group.
Time frame: during the 14 days of evaluation, including the safety call (day 14)
Population: The statistical analysis was by intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-122 | Number of Adverse Events | 28 adverse events |
| Krytantek Ofteno® | Number of Adverse Events | 31 adverse events |
p-value: 0.706Wilcoxon (Mann-Whitney)
Secondary
Number of Eyes With Epithelial Defects by Grade
The epithelial defects will be evaluated by means of two stains, green lissamine 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 8)
Population: The statistical analysis was per protocol (PP)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 0 | 20 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 1 | 2 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 2 | 0 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 3 | 0 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 4 | 0 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 0 | 22 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 1 | 0 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 2 | 0 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 3 | 0 eyes |
| PRO-122 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 4 | 0 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 2 | 0 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 0 | 16 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 0 | 22 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 1 | 4 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 4 | 0 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 2 | 4 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 1 | 2 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 3 | 0 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 3 | 0 eyes |
| Krytantek Ofteno® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 4 | 0 eyes |
Comparison: Green lissamine treatment groupsp-value: 0.081Chi-squared, Corrected
Comparison: Fluorescein treatment groupsp-value: 0.49Chi-squared, Corrected
Secondary
Participants With 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 8)
Population: the analysis was per protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRO-122 | Participants With Chemosis | 0 Participants |
| Krytantek Ofteno® | Participants With Chemosis | 0 Participants |
Secondary
Participants 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 8)
Population: the analysis was per protocol
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRO-122 | Participants With Conjunctival Hyperemia (CH) by Grade | Normal (0) | 10 Participants |
| PRO-122 | Participants With Conjunctival Hyperemia (CH) by Grade | Moderate (3) | 0 Participants |
| PRO-122 | Participants With Conjunctival Hyperemia (CH) by Grade | Very mild (1) | 0 Participants |
| PRO-122 | Participants With Conjunctival Hyperemia (CH) by Grade | Severe (4) | 0 Participants |
| PRO-122 | Participants With Conjunctival Hyperemia (CH) by Grade | Mild (2) | 1 Participants |
| Krytantek Ofteno® | Participants With Conjunctival Hyperemia (CH) by Grade | Severe (4) | 0 Participants |
| Krytantek Ofteno® | Participants With Conjunctival Hyperemia (CH) by Grade | Very mild (1) | 3 Participants |
| Krytantek Ofteno® | Participants With Conjunctival Hyperemia (CH) by Grade | Mild (2) | 0 Participants |
| Krytantek Ofteno® | Participants With Conjunctival Hyperemia (CH) by Grade | Moderate (3) | 0 Participants |
| Krytantek Ofteno® | Participants With Conjunctival Hyperemia (CH) by Grade | Normal (0) | 9 Participants |
p-value: 0.031Chi-squared, Corrected
Secondary
Visual Ability
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 or 1.0 in decimal and the worst 20/200 or 0.1 in decimal number. For the appropriate management of the data, the result of the fraction obtained from the snellen scale is transformed to decimals, in this case subjects close to or equal to 1.0 have better visual acuity while subjects close to or equal to 0.1 have worse visual acuity. The decimal equivalence scale is the result of the division of the fraction obtained in the Snellen chart. where 20/20 = 1.0; Do not confuse with Logmar scale where 20/20 = 0.0 Equivalences Snellen Scale = decimals: 20/200=0.1, 20/100=0.2, 20/50=0.4, 20/40=0.5, 20/30=0.66, 20/25=0.8, 20/20=1.0, etc.
Time frame: will be evaluated at the end of the treatment, at the final visit (day 8)
Population: the statistical analysis was per protocol (PP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-122 | Visual Ability | 0.949 Decimal score | Standard Deviation 0.11 |
| Krytantek Ofteno® | Visual Ability | 0.907 Decimal score | Standard Deviation 0.14 |
p-value: 0.253Wilcoxon (Mann-Whitney)
Other Pre-specified
Changes in Intraocular Pressure
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 8)
Population: the analysis was per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-122 | Changes in Intraocular Pressure | 12.32 mmHg | Standard Deviation 2.3 |
| Krytantek Ofteno® | Changes in Intraocular Pressure | 11.78 mmHg | Standard Deviation 1.8 |
p-value: 0.651Wilcoxon (Mann-Whitney)