Glaucoma
Conditions
Keywords
Travoprost, ophthalmic solution, Prostaglandin Analogues, Antiglaucoma drugs, glaucoma
Brief summary
Phase I clinical study, to evaluate the safety and tolerability of the ophthalmic solution PRO-179 compared with Travatan®, on the ocular surface of clinically healthy subjects. Goals: To evaluate the safety and tolerability of the formulation PRO-179 manufactured by Sophia Laboratories S.A. of C.V. on the ocular surface of clinically healthy subjects. Hypothesis:The ophthalmic solution PRO-179 presents a profile of safety and tolerability similar to Travatan® in healthy subjects. Methodology: Clinical trial Phase I, controlled, of parallel groups, double blind, with randomization.
Detailed description
Number of patients: n= 24, 12 subjects per group (both eyes). Main inclusion criteria: Clinically healthy subjects. duration: 10 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) or Fisher's exact. An alpha ≤ 0.05 will be considered significant.
Interventions
DRUGPRO 179
* Generic name: Travoprost * Distinctive denomination: Bristrio® (PRO-179) * Active principles: Travoprost 0.004%. * Pharmaceutical form: Ophthalmic solution * Presentation: multi-dose dropper bottle, 2.5 milliliters. * Prepared by: Sophia Laboratories, S.A. of C.V. * Description of the solution: transparent solution, free of visible particles. * Description of container: White bottle with 5 milliliters capacity, made of low density polyethylene.
DRUGTravatan 0.004 % Ophthalmic Solution
* Generic name: Travoprost * Distinctive denomination: Travatan® * Active ingredients: Travoprost 0.004% * Pharmaceutical form: Ophthalmic solution. * Presentation: multi-dose dropper bottle, 2.5 milliliters. * Prepared by: Alcon Laboratories Inc. * Description of the solution: transparent solution, free of visible particles. * Consult information to prescribe.
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 teams blinded / not blinded. 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. * Legend Exclusively for clinical studies * Date of Expiry.
Intervention model description
double blind, with randomization.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Be clinically healthy. * Have the ability to give their signed informed consent and show willingness to comply with the study procedures * Have an age between 18 to 45 years. * Indistinct sex. * Women should ensure the continued use of a hormonal contraceptive method or intrauterine device (IUD) during the study period. * Present 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. * Present visual ability 20/30 or better in both eyes. * Present vital signs within normal parameters. * Present intraocular pressure ≥10 and ≤ 21 mmHg.
Exclusion criteria
* Be a user of topical ophthalmic products of any kind. * Be a user of medicines, or herbal products, by any other route of administration, with the exception of hormonal contraceptives in the case of women. * In case of being a woman, being pregnant or breastfeeding. * Have participated in clinical research studies 90 days prior to inclusion in the present study. * Have previously participated in this same study. * Be a user of contact lenses and can not suspend their use during the study. * That they can not follow the lifestyle considerations described in section 6.2.2 * Having started the use of hormonal contraceptives or IUD, 30 days prior to inclusion in the present study. * Having a history of any chronic-degenerative disease. * Present inflammatory or infectious disease, active at the time of admission to the study. * Present injuries or unresolved traumas at the time of entering the study. * Having the antecedent of any type of eye surgery. * Having undergone surgical procedures, not ophthalmological, in the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Eye Comfort Index | will be evaluated at the end of the treatment, at the final visit (day 11) | 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.(0: None discomfort, 100: high discomfort). |
| Number of Participants With 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 11) | 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 the worst vision is 20/200, higher values represent a worst vision. The result of the Snellen chart has equivalents in an international logarithmic system called Logmar (logarithm of the minimum angle of resolution) for better understanding. Snellen Scale: 20/200, 20/100, 20/50, 20/40, 20/30, 20/25, 20/20, 20/15, 20/12, 20/10. Snellen / LogMAR equivalences: 20/200= 1.0, 20/100=0.7, 20/50=0.4, 20/40=0.3, 20/30=0.2, 20/25=0.1, 20/20=0.0, 20/15=0.13, 20/12=0.2, 20/10=-0.3, etc. |
| Number of Eyes of 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. |
| Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | 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. |
| Number of Eyes With Epithelial Defects by Grade | 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, lissamine green 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 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 |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-179 Dosage: 1 drop every 24 hours, at night, in both eyes.
PRO 179: o Generic name: Travoprost
* Distinctive denomination: Bristrio® (PRO-179)
* Active principles: Travoprost 0.004%.
* Pharmaceutical form: Ophthalmic solution
* Presentation: multi-dose dropper bottle, 2.5 milliliters.
* Prepared by: Sophia Laboratories, S.A. of C.V.
* Description of the solution: transparent solution, free of visible particles.
* Description of container: White bottle with 5 milliliters capacity, made of low density polyethylene. | 12 |
| Travatan® Dosage: 1 drop every 24 hours, at night, in both eyes.
Travatan 0.004 % Ophthalmic Solution: o Generic name: Travoprost
* Distinctive denomination: Travatan®
* Active ingredients: Travoprost 0.004%
* Pharmaceutical form: Ophthalmic solution.
* Presentation: multi-dose dropper bottle, 2.5 milliliters.
* Prepared by: Alcon Laboratories Inc.
* Description of the solution: transparent solution, free of visible particles.
* Consult information to prescribe. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Travatan® | Total | PRO-179 |
|---|---|---|---|
| Age, Continuous | 24.7 years STANDARD_DEVIATION 4.6 | 26.3 years STANDARD_DEVIATION 6.6 | 28.2 years STANDARD_DEVIATION 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 | 8 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 12 Participants | 8 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 | 10 / 12 | 11 / 12 |
| serious Total, serious adverse events | 1 / 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.(0: None discomfort, 100: high discomfort).
Time frame: will be evaluated at the end of the treatment, at the final visit (day 11)
Population: the analysis was per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-179 | Eye Comfort Index | 26.61 score on a scale | Standard Deviation 11.3 |
| Travatan® | Eye Comfort Index | 28.97 score on a scale | Standard Deviation 7.9 |
Primary
Number of Participants With 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 analysis was carried out by intention to treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRO-179 | Number of Participants With Adverse Events | 10 Participants |
| Travatan® | Number of Participants With Adverse Events | 11 Participants |
p-value: 1Fisher Exact
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 11)
Population: the analysis was per protocol
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| PRO-179 | Number of Eyes of Chemosis | 0 eyes |
| Travatan® | Number of Eyes of Chemosis | 0 eyes |
Secondary
Number of Eyes With Epithelial Defects by Grade
The epithelial defects will be evaluated by means of two stains, lissamine green 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 11)
Population: The analysis was per protocol
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 4 | 0 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 0 | 22 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 0 | 20 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 2 | 0 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 1 | 2 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 3 | 0 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 2 | 0 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 3 | 0 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 4 | 0 eyes |
| PRO-179 | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 1 | 0 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 4 | 0 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 0 | 23 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 1 | 1 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 2 | 0 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 3 | 0 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Green lissamine grade 4 | 0 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 0 | 20 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 1 | 4 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 3 | 0 eyes |
| Travatan® | Number of Eyes With Epithelial Defects by Grade | Fluorescein grade 2 | 0 eyes |
Comparison: Lissamine green treatment groupsp-value: 1Fisher Exact
Comparison: Fluorescein treatment groupsp-value: 0.667Fisher Exact
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 11)
Population: the analysis was per protocol
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| PRO-179 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Very mild (1) | 2 eyes |
| PRO-179 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Moderate (3) | 0 eyes |
| PRO-179 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Mild (2) | 6 eyes |
| PRO-179 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Severe (4) | 0 eyes |
| PRO-179 | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Normal (0) | 14 eyes |
| Travatan® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Severe (4) | 0 eyes |
| Travatan® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Normal (0) | 16 eyes |
| Travatan® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Very mild (1) | 2 eyes |
| Travatan® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Mild (2) | 6 eyes |
| Travatan® | Percentage of Eyes With Conjunctival Hyperemia (CH) by Grade | Moderate (3) | 0 eyes |
Comparison: the analysis was per protocolp-value: 0.977Chi-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 and the worst vision is 20/200, higher values represent a worst vision. The result of the Snellen chart has equivalents in an international logarithmic system called Logmar (logarithm of the minimum angle of resolution) for better understanding. Snellen Scale: 20/200, 20/100, 20/50, 20/40, 20/30, 20/25, 20/20, 20/15, 20/12, 20/10. Snellen / LogMAR equivalences: 20/200= 1.0, 20/100=0.7, 20/50=0.4, 20/40=0.3, 20/30=0.2, 20/25=0.1, 20/20=0.0, 20/15=0.13, 20/12=0.2, 20/10=-0.3, etc.
Time frame: will be evaluated at the end of the treatment, at the final visit (day 11)
Population: the analysis was per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-179 | Visual Ability | 0.0 LogMAR | Standard Deviation 0 |
| Travatan® | Visual Ability | 0.0 LogMAR | Standard Deviation 0 |
p-value: 1Wilcoxon (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 11)
Population: the analysis was per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-179 | Changes in Intraocular Pressure | 11.95 mmHg | Standard Deviation 1.6 |
| Travatan® | Changes in Intraocular Pressure | 10.71 mmHg | Standard Deviation 1.5 |
p-value: 0.019Wilcoxon (Mann-Whitney)