Ocular Hypertension, Primary Open Angle Glaucoma
Conditions
Keywords
Latanoprost, Glaucoma, Ocular hypertension, Crossover study
Brief summary
Aim: To demonstrate the non-inferiority of the PRO-067 ophthalmic solution manufactured by Laboratorios Sophia S.A. de C.V. versus GAAP 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 60 patients will be assigned to receive the ophthalmic solution: GAAP Ofteno ® (latanoprost 0.005%) 1 drop per day (QD) during 30 days and the second sequence 60 patients will be assigned to receive the ophthalmic solution: PRO-067 1 drop QD during 30 days in the same period. Washout period: 21 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 Latanoprost 0.005% (GAAP Ofteno®, Laboratorios Sophia, Mexico) and the other one treated with PRO-067 ophthalmic solution. Patients will receive 1 drop per day (QD) into the lower conjunctival sac of either formulations and were examined at days: 1, 15, 30, 45 ad 60 after initiation of treatment. A phone call security at day 75 will be performed. Primary efficacy outcome: To evaluate the efficacy of PRO-067 versus GAAP 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-067
1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.
DRUGGAAP Ofteno®
1 drop QD during 30 days Active comparator, reference medication.
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female or male * Age: ≥18 years old * Patients with primary open angle glaucoma with mild to moderate damage or ocular hypertension that were sufficiently controlled with GAAP Ofteno® (latanoprost 0.005%) within the last 60 days * Signed Informed Consent Form
Exclusion criteria
* Subjects with unique eye * Subjects with visual acuity \< 20/200 * Another kind of glaucoma disease different to primary open angle glaucoma * corneal disturbances with impossibility to measure the intraocular pressure * retinal alterations without control or progressive retinal disease with high risk to lost vision
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Target Intraocular Pressure (TIOP) | the baseline visit (day 0), Cross Over Visit (day 30) and the final visit (day 60) for both sequences | Target Intraocular Pressure (TIOP): Efficacy of experimental drug or active comparator to maintain the IOP in 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.The upper limit of intraocular pressure is: TIOP + 2 mmHg. The measurement of the TIOP in each treatment period. |
| Number of Adverse Events. | it is evaluated from the baseline visit (day 1) to the security call (day 75) | the two periods of PRO-067 of each sequence were grouped as well as those of GAAP to form two comparative groups of adverse events in each intervention. (PRO-067 vs. GAAP ofteno). The number of adverse events presented throughout the study was evaluated with each study drug to make the comparison between groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tearing | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | The tearing will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences. |
| Percentage of Ocular Burning | at the basal visit (day 1) crossover visit (day 30) and final visit (day 60) | the ocular burning of the study subjects was evaluated, during the baseline, crossover and final visit, the variable was described as present or absent, according to the case, in both groups. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences. |
| Percentage of Participants With Hyperemia | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | the hyperemia of the study subjects was evaluated, during the baseline, crossover and final visit, the variable was described as a scale of: absent, very mild, mild, moderate and severe, according to the case, in both groups. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences. |
| Percentage of Participants With Chemosis | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | The chemosis will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences. |
| Percentage of Participants With Foreign Body Sensation | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | The foreign body sensation will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences. |
Countries
Mexico
Participant flow
Recruitment details
The study raised 120 research subjects, only 116 were selected, 2 left the study before being evaluated for a total of 114. However, 7 subjects were eliminated by: closure of center 1, without monitoring 2, by loss of follow-up 2, non-compliance with inclusion criteria 1 and failure of scrutiny 1, leaving a total of 107 randomized research subjects
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 (PRO-067) 60 study subjects will be allocated to receive PRO-067 QD for 30 days, after which they will be crossed over to the other medication (GAAP Ofteno®) for another 30 days. The Intraocular pressure-reducing effect of the medications will be assessed by the reduction in IOP after each medication compared to baseline.
Washout period: 21 hours
PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.
GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication. | 51 |
| Sequence 2 (GAAP Ofteno®) 60 study subjects will be allocated to receive GAAP Ofteno® QD for 30 days, after which they will be crossed over to the other medication (PRO-067) for another 30 days. The Intraocular pressure-reducing effect of the medications will be assessed by the reduction in IOP after each medication compared to baseline.
Washout period: 21 hours
PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.
GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication. | 56 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 6 |
Baseline characteristics
| Characteristic | Sequence 1 (PRO-067) | Sequence 2 (GAAP Ofteno®) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 24 Participants | 45 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 32 Participants | 62 Participants |
| Race/Ethnicity, Customized Hispanic | 51 Participants | 56 Participants | 107 Participants |
| Sex: Female, Male Female | 36 Participants | 47 Participants | 83 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 56 |
| other Total, other adverse events | 24 / 51 | 20 / 56 |
| serious Total, serious adverse events | 0 / 51 | 0 / 56 |
Outcome results
Primary
Number of Adverse Events.
the two periods of PRO-067 of each sequence were grouped as well as those of GAAP to form two comparative groups of adverse events in each intervention. (PRO-067 vs. GAAP ofteno). The number of adverse events presented throughout the study was evaluated with each study drug to make the comparison between groups.
Time frame: it is evaluated from the baseline visit (day 1) to the security call (day 75)
Population: intention-to-treat (ITT), all those subjects who received at least one dose of the investigational drugs were considered for the statistical analysis, having a total of 107 cases by intention to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A (PRO-067- GAAP Ofteno®) | Number of Adverse Events. | 24 adverse events |
| Sequence B (GAAP Ofteno® - PRO-067) | Number of Adverse Events. | 20 adverse events |
p-value: 0.329Chi-squared
Primary
Target Intraocular Pressure (TIOP)
Target Intraocular Pressure (TIOP): Efficacy of experimental drug or active comparator to maintain the IOP in 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.The upper limit of intraocular pressure is: TIOP + 2 mmHg. The measurement of the TIOP in each treatment period.
Time frame: the baseline visit (day 0), Cross Over Visit (day 30) and the final visit (day 60) for both sequences
Population: by Protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A (PRO-067- GAAP Ofteno®) | Target Intraocular Pressure (TIOP) | final visit | 13.99 mmHg | Standard Deviation 2.46 |
| Sequence A (PRO-067- GAAP Ofteno®) | Target Intraocular Pressure (TIOP) | baseline visit | 14.25 mmHg | Standard Deviation 2.37 |
| Sequence A (PRO-067- GAAP Ofteno®) | Target Intraocular Pressure (TIOP) | Cross over visit | 13.85 mmHg | Standard Deviation 2.07 |
| Sequence B (GAAP Ofteno® - PRO-067) | Target Intraocular Pressure (TIOP) | Cross over visit | 13.92 mmHg | Standard Deviation 2.17 |
| Sequence B (GAAP Ofteno® - PRO-067) | Target Intraocular Pressure (TIOP) | final visit | 14.07 mmHg | Standard Deviation 2.37 |
| Sequence B (GAAP Ofteno® - PRO-067) | Target Intraocular Pressure (TIOP) | baseline visit | 14.04 mmHg | Standard Deviation 2.43 |
p-value: 0.861t-test, 2 sided
p-value: 0.89t-test, 2 sided
Secondary
Percentage of Ocular Burning
the ocular burning of the study subjects was evaluated, during the baseline, crossover and final visit, the variable was described as present or absent, according to the case, in both groups. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time frame: at the basal visit (day 1) crossover visit (day 30) and final visit (day 60)
Population: analysis by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Ocular Burning | Crossover visit | 03.8 percentage of Ocular burning |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Ocular Burning | Final visit | 10.3 percentage of Ocular burning |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Ocular Burning | basal visit | 20.7 percentage of Ocular burning |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Ocular Burning | Crossover visit | 25.0 percentage of Ocular burning |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Ocular Burning | basal visit | 19.6 percentage of Ocular burning |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Ocular Burning | Final visit | 16.1 percentage of Ocular burning |
p-value: 0.388Chi-squared, Corrected
Secondary
Percentage of Participants With Chemosis
The chemosis will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time frame: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Population: Analysis by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Chemosis | final visit (day 60) | 0 percentage of patients with chemosis |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Chemosis | basal visit (day 1) | 3.4 percentage of patients with chemosis |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Chemosis | Crossover visit (day 30) | 0 percentage of patients with chemosis |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Chemosis | final visit (day 60) | 0 percentage of patients with chemosis |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Chemosis | basal visit (day 1) | 7.1 percentage of patients with chemosis |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Chemosis | Crossover visit (day 30) | 0 percentage of patients with chemosis |
p-value: 0Chi-squared, Corrected
Secondary
Percentage of Participants With Foreign Body Sensation
The foreign body sensation will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time frame: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Population: Analysis by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Foreign Body Sensation | final visit (day 60) | 17.2 percentage of patients with Foreign body |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Foreign Body Sensation | basal visit (day 1) | 20.7 percentage of patients with Foreign body |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Foreign Body Sensation | Crossover visit (day 30 | 24.1 percentage of patients with Foreign body |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Foreign Body Sensation | Crossover visit (day 30 | 30.4 percentage of patients with Foreign body |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Foreign Body Sensation | basal visit (day 1) | 37.5 percentage of patients with Foreign body |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Foreign Body Sensation | final visit (day 60) | 30.4 percentage of patients with Foreign body |
p-value: 0.125Chi-squared, Corrected
Secondary
Percentage of Participants With Hyperemia
the hyperemia of the study subjects was evaluated, during the baseline, crossover and final visit, the variable was described as a scale of: absent, very mild, mild, moderate and severe, according to the case, in both groups. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time frame: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Population: Analysis by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Final visit Very Mild | 67.2 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Basal Visit Moderate | 5.2 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Cross Over Visit Moderate | 1.7 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Cross Over Visit Very Mild | 60.3 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Cross Over Visit Mild | 37.9 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Final Visit Mild | 32.8 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Basal Visit Mild | 41.4 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Final Visit Moderate | 0 percentage of patients with hyperemia |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Hyperemia | Basal Visit Very Mild | 53.4 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Final Visit Moderate | 7.1 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Cross Over Visit Mild | 44.6 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Cross Over Visit Moderate | 3.6 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Final visit Very Mild | 69.6 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Basal Visit Very Mild | 50.0 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Basal Visit Mild | 43.9 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Basal Visit Moderate | 4.4 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Cross Over Visit Very Mild | 51.8 percentage of patients with hyperemia |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Hyperemia | Final Visit Mild | 23.2 percentage of patients with hyperemia |
p-value: 0.039Chi-squared
Secondary
Percentage of Participants With Tearing
The tearing will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time frame: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Population: Analysis by protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Tearing | Basal visit (day 1) | 8.6 percentage of patients with tearing |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Tearing | Crossover visit (day 30) | 8.6 percentage of patients with tearing |
| Sequence A (PRO-067- GAAP Ofteno®) | Percentage of Participants With Tearing | Final visit (day 60) | 3.4 percentage of patients with tearing |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Tearing | Basal visit (day 1) | 5.4 percentage of patients with tearing |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Tearing | Crossover visit (day 30) | 10.7 percentage of patients with tearing |
| Sequence B (GAAP Ofteno® - PRO-067) | Percentage of Participants With Tearing | Final visit (day 60) | 7.1 percentage of patients with tearing |
p-value: 0.434Chi-squared, Corrected