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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PRO-122 | Experimental | - Dosage: 1 drop every 12 hours, in both eyes |
|
| Krytantek Ofteno® | Active Comparator | - Dosage: 1 drop every 12 hours, in both eyes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRO-122 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | during the 14 days of evaluation, including the safety call (day 14) |
| 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. | will be evaluated at the end of the treatment, at the final visit (day 8) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | will be evaluated at the end of the treatment, at the final visit (day 8) |
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.
Visual ability 20/30 or better in both eyes.
Vital signs within normal parameters.
Intraocular pressure ≥10 and ≤ 21 mmHg.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Leopoldo Baiza Durán, MD | Laboratorios Sophia S.A de C.V. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unidad ClÃnica de Bioequivalencia, S. de R.L. de C.V. | Guadalajara | Jalisco | 44190 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34707360 | Derived | Munoz-Villegas P, Navarro-Sanchez AA, Sanchez-Rios A, Olvera-Montano O, Baiza-Duran LM. Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials. Ther Clin Risk Manag. 2021 Oct 21;17:1123-1134. doi: 10.2147/TCRM.S331294. eCollection 2021. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The statistical analysis was by intention to treat (ITT) | Posted | Number | adverse events | during the 14 days of evaluation, including the safety call (day 14) |
|
Adverse events were monitored throughout the study, which lasted about 4 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ocular burning | Eye disorders | 22.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| PhD. Ricardo Llamas | Laboratorios Sophia | +52 (33) 3001 4200 | 1259 | ricardo.llamas@sophia.com.mx |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 22, 2018 | May 24, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005901 | Glaucoma |
| ID | Term |
|---|---|
| D009798 | Ocular Hypertension |
| D005128 | Eye Diseases |
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Phase I clinical trial, controlled, parallel group, double blind, randomized.
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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:
|
| Krytantek Ofteno® | Drug |
|
|
|
| will be evaluated at the end of the treatment, at the final visit (day 8) |
| 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. | will be evaluated at the end of the treatment, at the final visit (day 8) |
| 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. | will be evaluated at the end of the treatment, at the final visit (day 8) |
| 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. | will be evaluated at the end of the treatment, at the final visit (day 8) |
| 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
- 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. |
|
|
|
| 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. | Analysis per protocol (PP) | Posted | Mean | Standard Deviation | units on a scale | will be evaluated at the end of the treatment, at the final visit (day 8) |
|
|
|
|
| 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. | The statistical analysis was per protocol (PP) | Posted | Number | eyes | will be evaluated at the end of the treatment, at the final visit (day 8) | eyes | eyes |
|
|
|
|
| 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. | the statistical analysis was per protocol (PP) | Posted | Mean | Standard Deviation | Decimal score | will be evaluated at the end of the treatment, at the final visit (day 8) |
|
|
|
|
| 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. | the analysis was per protocol | Posted | Count of Participants | Participants | will be evaluated at the end of the treatment, at the final visit (day 8) |
|
|
|
|
| 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. | the analysis was per protocol | Posted | Count of Participants | Participants | will be evaluated at the end of the treatment, at the final visit (day 8) |
|
|
|
| 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 | the analysis was per protocol | Posted | Mean | Standard Deviation | mmHg | will be evaluated at the end of the treatment, at the final visit (day 8) |
|
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 11 |
| 12 |
| EG001 | 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. | 0 | 12 | 0 | 12 | 11 | 12 |
| nonspecific conjunctivitis | Eye disorders | 22.0 | Non-systematic Assessment |
|
| herpes labialis | Skin and subcutaneous tissue disorders | 22.0 | Non-systematic Assessment |
|
| pruritus | Eye disorders | 22.0 | Non-systematic Assessment |
|
| ocular hyperemia | Eye disorders | 22.0 | Non-systematic Assessment |
|
| feeling of sticky eyes | Eye disorders | 22.0 | Non-systematic Assessment |
|
| decreased visual acuity | Eye disorders | 22.0 | Non-systematic Assessment |
|
| headache | Nervous system disorders | 22.0 | Non-systematic Assessment |
|
| rhinitis | Respiratory, thoracic and mediastinal disorders | 22.0 | Non-systematic Assessment |
|
| clogged ear | Ear and labyrinth disorders | 22.0 | Non-systematic Assessment |
|
| stomach ache | Gastrointestinal disorders | 22.0 | Non-systematic Assessment |
|
| foreign body sensation in eye | Eye disorders | 22.0 | Non-systematic Assessment |
|
| Dry Eye | Eye disorders | 22.0 | Non-systematic Assessment |
|
| eyestrain | Eye disorders | 22.0 | Non-systematic Assessment |
|
| dysgeusia | Gastrointestinal disorders | 22.0 | Non-systematic Assessment |
|
| tearing | Eye disorders | 22.0 | Non-systematic Assessment |
|
| dizziness | Gastrointestinal disorders | 22.0 | Non-systematic Assessment |
|
| earache | Ear and labyrinth disorders | 22.0 | Non-systematic Assessment |
|
only the sponsor has the decision to disseminate or publish the information obtained from the investigation and the PIs involved must submit a formal request to the sponsor if they are willing to disseminate or publish such information, they may only publish them if they have the written authorization of the sponsor (Laboratoios Sophia S.A. de C.V.).
| Green lissamine grade 2 |
|
| Green lissamine grade 3 |
|
| Green lissamine grade 4 |
|
| Fluorescein grade 0 |
|
| Fluorescein grade 1 |
|
| Fluorescein grade 2 |
|
| Fluorescein grade 3 |
|
| Fluorescein grade 4 |
|
| 0.490 |
| Other |
| Mild (2) |
|
| Moderate (3) |
|
| Severe (4) |
|