Primary Open Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
timolol, dorzolamide, brimonidine, Glaucoma, Ocular hypertension
Brief summary
Aim: To demonstrate the non-inferiority of the PRO-122 ophthalmic solution manufactured by Laboratorios Sophia S.A. de C.V. versus Krytantek Ofteno® ophthalmic solution like hypotensive therapy in subjects with primary open angle glaucoma or ocular hypertension. Study design: a multicentric, prospective, crossover (2x2), double blind clinical study. Sample size: one hundred patients with primary open angle glaucoma or ocular hypertension. Patients in the period 1: In the first sequence 30 patients will be assigned to receive the ophthalmic solution: Krytantek Ofteno ® (timolol 0.5%%/brimonidine 0.2%/dorzolamide 2%) 1 drop B.I.D. during 30 days and the second sequence 30 patients will be assigned to receive the ophthalmic solution: PRO-122 1 drop B.I.D. during 30 days in the same period. Washout period: 20 hours. Patients in the period 2: the pharmacological intervention change to the opposite therapy for 30 days
Detailed description
The American Academy of Ophthalmology Glaucoma Panel: The primary open angle glaucoma (POAG) is a progressive, chronic optic neuropathy in adults in which intraocular pressure (IOP) and other currently unknown factors contribute to damage and in which, in the absence of other identifiable causes, there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. This condition is associated with an anterior chamber angle that is open by gonioscopic appearance. This is a multicentric, crossover, double blind and prospective clinical study. The investigators will include patients with confirmed diagnosis of primary open-angle glaucoma or ocular hypertension, with target intraocular pressure (TIOP) within a range at which a patient is likely to remain stable or at which worsening of glaucoma will be slow enough that the risk of additional intervention is not justified. Patients will be randomly divided into 2 groups, one of them treated with a known formulation of timolol 0.5%/brimonidine 0.2%/dorzolamide 2% (Krytantek Ofteno®, Laboratorios Sophia, Mexico) and the other one treated with PRO-122 ophthalmic solution. Patients will receive 1 drop B.I.D. into the lower conjunctival sac of either formulations and were examined at days: 1, 15, 30, 45 and 61 after initiation of treatment. A phone call security at day 75 will be performed. Primary efficacy outcome: To evaluate the efficacy of PRO-122 versus Krytantek Ofteno® instilled onto the ocular surface in subjects with primary open angle glaucoma (POAG) or ocular hypertension (HTO), to control and maintenance of the target intraocular pressure (TIOP).
Interventions
DRUGPRO-122
1 drop every 12 hours for 30 days of alternating treatment with 30 days
1 drop every 12 hours for 30 days of alternating treatment with 30 days
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masking will be carried out using identical boxes in the primary package in both groups. Blinding for the research subject and the investigator will be carried out by using labels containing the assignation number, which will replace the original labels in the case of the comparator. Due to the nature of the primary containers of the research products, single-dose vials and multidose bottle, it is not possible to use identical labels.
Intervention model description
60 subjects with diagnosis of open angle primary glaucoma with mild, moderate or severe damage and / or with intraocular hypertension users of Krytantek Ofteno® at least two previous months and are under control Of the corresponding IOP target. a study group A or B will be randomly assigned, in group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be evaluated again and switched from therapy to solution PRO-122 which will be used for 30 days until the 60th day, date of the final visit. In the case of those assigned to group B on day 1, the change to PRO-122 solution will be made for 30 continuous days until the date of revision on day 30, the day on which treatment with Krytantek Ofteno® will be restored to continue until the Day 60 for the final evaluation. The selected subjects will be observed for 60 days.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * male or female. * obtained in the external consultation. * With diagnosis primary of open-angle glaucoma and / or hypertension classified as mild, moderate or severe glaucomatous damage, users of Krytantek Ofteno® at least two months prior to inclusion and under control of the target IOP. * informed consent.
Exclusion criteria
General Criteria 1. Subjects with topical or systemic medication that interferes decisively in the results of the study. (Such as topical immunomodulators, lacrimal point tamponade, corticosteroids, ocular hypotensives other than those listed above, artificial tears with preservative). 2. Subjects (female) with an active sex life who are not using a contraceptive method. 3. Female Subjects in pregnancy or breastfeeding. 4. Female subjects with positive urine pregnancy test. 5. Positive drug addiction (verbal interrogation). 6. Subjects who have participated in any clinical research study in the last 40 days. 7. Legally or mentally disabled subjects to give informed consent for their participation in this study. 8. Subjects who can not comply with the appointments or with all the requirements of the protocol. Ophthalmologic criteria 1. Subject with only one eye with vision. 2. Subjects with visual capacity 20/200 or worse. 3. Subjects with a narrow-angle history without treatment, with or without total or partial closure of the angle in either eye. 4. Subjects with corneal abnormalities that prevent applanation tonometry. 5. Subjects with ocular surgery or ocular trauma 6 months prior to inclusion. 6. Any ocular laser surgery 3 months prior. 7. Any uncontrolled or progressive retinal disease. 8. Inflammatory diseases of any kind. 9. Contact lens wearers. 10. Subjects with a history of hypersensitivity to any of the ingredients of the research product or its analogues.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure (IOP) | Change from Baseline intraocular pressure at day 30 and 60. | Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg. The change between the IOP of both groups was compared (sequence 1 versus sequence 2) of the data obtained at the end of each period (day 30 and day 60). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity (VA) | Visual Acuity at Baseline (day 1) crossover visit (day 30) and final visit (day 60) | The VA will be evaluated basally, without refractive correction with the Snellen chart. A Snellen chart is placed at a standard distance: 20 ft. At this distance, the symbols on the line representing normal acuity subtend. This line, designated 20/20 is the smallest line that a person with normal acuity can read at a distance of 20fs. the scale consists of 11 lines of letters of different size, the size of the letter gives a fractional value according to the visual acuity of the patient, the value is inversely proportional to the visual acuity, if the denominator is greater the visual acuity will be less. Line 1: 20/200 Line 2: 20/100, Line 3: 20/70, line 4: 20/50, line 5: 20/40, Line 6: 20/30, line 7: 20/25, Line 8: 20/20, line 9: 20/15, line 10: 20/13, line 11: 20/10. the differences between groups in the basal, cross over and final visit will be evaluated. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Chemosis | Baseline (day 1) crossover visit (day 30) and final visit (day 60) | Chemosis: qualitative ordinal variable, will be evaluated by the presence or absence of it and the percentage of affected by group will be reported. |
| Eye Burning | Baseline (day 1) crossover visit (day 30) and final visit (day 60) | Eye ocular burning will be evaluated by the presence or absence of it and the number of affected by group will be reported. |
| Adverse Events | 75 days, includes the security call | The presence of adverse events by percentage between groups will be evaluated. the scale is present or absent. |
| Number of Eyes With Foreign Body Sensation | Baseline (day 1) crossover visit (day 30) and final visit (day 60) | Foreign body sensation will be evaluated by the presence or absence of it and the number of affected by group will be reported. |
| Number of Eyes With Tearing | Baseline (day 1) crossover visit (day 30) and final visit (day 60) | Tearing will be evaluated by the presence or absence of it and the number of affected by group will be reported |
| Conjunctival Hyperemia | Baseline (day 1) crossover visit (day 30) and final visit (day 60) | the conjunctival hyperemia will be evaluated by the presence or absence of it and the percentage of affected by group will be reported. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit.
PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days | 30 |
| Group B In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit.
PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 6 | 3 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Continuous | 68.43 years STANDARD_DEVIATION 8.86 | 64.37 years STANDARD_DEVIATION 12.84 | 66.44 years STANDARD_DEVIATION 11.17 |
| Race/Ethnicity, Customized hispanic | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Female | 24 Participants | 21 Participants | 45 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 12 / 60 | 8 / 60 |
| serious Total, serious adverse events | 0 / 60 | 1 / 60 |
Outcome results
Primary
Intraocular Pressure (IOP)
Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg. The change between the IOP of both groups was compared (sequence 1 versus sequence 2) of the data obtained at the end of each period (day 30 and day 60).
Time frame: Change from Baseline intraocular pressure at day 30 and 60.
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Intraocular Pressure (IOP) | basal visit (day 1) | 13.60 mmHg | Standard Deviation 2.9 |
| Sequence A | Intraocular Pressure (IOP) | Crossover visit (day 30) | 13.19 mmHg | Standard Deviation 3.2 |
| Sequence A | Intraocular Pressure (IOP) | Final visit (day 60) | 12.60 mmHg | Standard Deviation 3 |
| Sequence B | Intraocular Pressure (IOP) | basal visit (day 1) | 12.13 mmHg | Standard Deviation 1.8 |
| Sequence B | Intraocular Pressure (IOP) | Crossover visit (day 30) | 11.80 mmHg | Standard Deviation 2.1 |
| Sequence B | Intraocular Pressure (IOP) | Final visit (day 60) | 11.24 mmHg | Standard Deviation 1.6 |
p-value: 0.013t-test, 2 sided
p-value: 0.001t-test, 2 sided
p-value: 0.05t-test, 2 sided
Secondary
Visual Acuity (VA)
The VA will be evaluated basally, without refractive correction with the Snellen chart. A Snellen chart is placed at a standard distance: 20 ft. At this distance, the symbols on the line representing normal acuity subtend. This line, designated 20/20 is the smallest line that a person with normal acuity can read at a distance of 20fs. the scale consists of 11 lines of letters of different size, the size of the letter gives a fractional value according to the visual acuity of the patient, the value is inversely proportional to the visual acuity, if the denominator is greater the visual acuity will be less. Line 1: 20/200 Line 2: 20/100, Line 3: 20/70, line 4: 20/50, line 5: 20/40, Line 6: 20/30, line 7: 20/25, Line 8: 20/20, line 9: 20/15, line 10: 20/13, line 11: 20/10. the differences between groups in the basal, cross over and final visit will be evaluated.
Time frame: Visual Acuity at Baseline (day 1) crossover visit (day 30) and final visit (day 60)
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Visual Acuity (VA) | basal visit (day 1) | 38.31 score on a scale | Standard Error 3.577 |
| Sequence A | Visual Acuity (VA) | Crossover visit (day 30) | 36.85 score on a scale | Standard Error 3.806 |
| Sequence A | Visual Acuity (VA) | Final visit (day 60) | 38.98 score on a scale | Standard Error 3.717 |
| Sequence B | Visual Acuity (VA) | basal visit (day 1) | 39.48 score on a scale | Standard Error 3.742 |
| Sequence B | Visual Acuity (VA) | Crossover visit (day 30) | 40.43 score on a scale | Standard Error 3.753 |
| Sequence B | Visual Acuity (VA) | Final visit (day 60) | 35.50 score on a scale | Standard Error 3.402 |
p-value: 0.823t-test, 2 sided
p-value: 0.507t-test, 2 sided
p-value: 0.495t-test, 2 sided
Other Pre-specified
Adverse Events
The presence of adverse events by percentage between groups will be evaluated. the scale is present or absent.
Time frame: 75 days, includes the security call
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases. statistical analysis by intention to treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A | Adverse Events | mild | 55.6 percentage of adverse events |
| Sequence A | Adverse Events | moderate | 44.4 percentage of adverse events |
| Sequence A | Adverse Events | severe | 0 percentage of adverse events |
| Sequence B | Adverse Events | mild | 18.2 percentage of adverse events |
| Sequence B | Adverse Events | moderate | 72.7 percentage of adverse events |
| Sequence B | Adverse Events | severe | 9.1 percentage of adverse events |
p-value: 0.085Chi-squared
Other Pre-specified
Chemosis
Chemosis: qualitative ordinal variable, will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.
Time frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60)
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A | Chemosis | basal visit (day 1) | 0 percentage of chemosis |
| Sequence A | Chemosis | Crossover visit (day 30) | 0 percentage of chemosis |
| Sequence A | Chemosis | Final visit (day 60) | 0 percentage of chemosis |
| Sequence B | Chemosis | basal visit (day 1) | 3.7 percentage of chemosis |
| Sequence B | Chemosis | Crossover visit (day 30) | 3.7 percentage of chemosis |
| Sequence B | Chemosis | Final visit (day 60) | 0 percentage of chemosis |
p-value: 0.497Chi-squared, Corrected
p-value: 0.497Chi-squared, Corrected
p-value: 0Chi-squared, Corrected
Other Pre-specified
Conjunctival Hyperemia
the conjunctival hyperemia will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.
Time frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60)
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A | Conjunctival Hyperemia | basal visit (day 1) | 39.6 percentage of eyes |
| Sequence A | Conjunctival Hyperemia | Crossover visit (day 30) | 37.5 percentage of eyes |
| Sequence A | Conjunctival Hyperemia | Final visit (day 60) | 20.8 percentage of eyes |
| Sequence B | Conjunctival Hyperemia | basal visit (day 1) | 11.1 percentage of eyes |
| Sequence B | Conjunctival Hyperemia | Crossover visit (day 30) | 25.9 percentage of eyes |
| Sequence B | Conjunctival Hyperemia | Final visit (day 60) | 13.0 percentage of eyes |
p-value: 0.001Fisher Exact
p-value: 0.148Fisher Exact
p-value: 0.212Fisher Exact
Other Pre-specified
Eye Burning
Eye ocular burning will be evaluated by the presence or absence of it and the number of affected by group will be reported.
Time frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60)
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A | Eye Burning | basal visit (day 1) | 16 number of eye burning |
| Sequence A | Eye Burning | Crossover visit (day 30) | 12 number of eye burning |
| Sequence A | Eye Burning | Final visit (day 60) | 14 number of eye burning |
| Sequence B | Eye Burning | basal visit (day 1) | 18 number of eye burning |
| Sequence B | Eye Burning | Crossover visit (day 30) | 18 number of eye burning |
| Sequence B | Eye Burning | Final visit (day 60) | 19 number of eye burning |
p-value: 1Chi-squared
p-value: 0.391Chi-squared
p-value: 0.534Chi-squared
Other Pre-specified
Number of Eyes With Foreign Body Sensation
Foreign body sensation will be evaluated by the presence or absence of it and the number of affected by group will be reported.
Time frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60)
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A | Number of Eyes With Foreign Body Sensation | basal visit (day 1) | 14 eyes |
| Sequence A | Number of Eyes With Foreign Body Sensation | Crossover visit (day 30) | 14 eyes |
| Sequence A | Number of Eyes With Foreign Body Sensation | Final visit (day 60) | 5 eyes |
| Sequence B | Number of Eyes With Foreign Body Sensation | basal visit (day 1) | 14 eyes |
| Sequence B | Number of Eyes With Foreign Body Sensation | Crossover visit (day 30) | 16 eyes |
| Sequence B | Number of Eyes With Foreign Body Sensation | Final visit (day 60) | 7 eyes |
p-value: 0.825Chi-squared
p-value: 1Chi-squared
p-value: 0.765Chi-squared
Other Pre-specified
Number of Eyes With Tearing
Tearing will be evaluated by the presence or absence of it and the number of affected by group will be reported
Time frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60)
Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A | Number of Eyes With Tearing | basal visit (day 1) | 9 eyes |
| Sequence A | Number of Eyes With Tearing | Crossover visit (day 30) | 8 eyes |
| Sequence A | Number of Eyes With Tearing | Final visit (day 60) | 7 eyes |
| Sequence B | Number of Eyes With Tearing | basal visit (day 1) | 2 eyes |
| Sequence B | Number of Eyes With Tearing | Crossover visit (day 30) | 9 eyes |
| Sequence B | Number of Eyes With Tearing | Final visit (day 60) | 9 eyes |
p-value: 0.023Chi-squared, Corrected
p-value: 1Chi-squared
p-value: 0.793Chi-squared