Non-inferiority of PRO-067 Ophthalmic Solution vs GAAP Ofteno® in Glaucoma or Ocular Hypertension

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Multicentric, Prospective, Crossover, Double Blind Clinical Study to Evaluate the Non-inferiority of PRO-067 an Ophthlamic Solution Manufactured by Laboratorios Sophia S.A.de C.V., Previous Treatment With GAAP Ofteno ®, in Subjects With Primary Open-angle Glaucoma (POAG) or Ocular Hypertension (OHT): COMPLIANCE Study

Conditions
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Primary Open Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: PRO-067
* Drug: GAAP Ofteno®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1 (PRO-067)<br>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 | Drug: PRO-067<br>* 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.<br>* Other names: SOPH067-0914/III;Drug: GAAP Ofteno®<br>* 1 drop QD during 30 days Active comparator, reference medication.<br>* Other names: Latanoprost 0.005% , prostaglandin, antiglaucoma medication;|
| Active Comparator: Sequence 2 (GAAP Ofteno®)<br>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 | Drug: PRO-067<br>* 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.<br>* Other names: SOPH067-0914/III;Drug: GAAP Ofteno®<br>* 1 drop QD during 30 days Active comparator, reference medication.<br>* Other names: Latanoprost 0.005% , prostaglandin, antiglaucoma medication;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | the baseline visit (day 0), Cross Over Visit (day 30) and the final visit (day 60) for both sequences | 
| 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. | it is evaluated from the baseline visit (day 1) to the security call (day 75) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | at the basal visit (day 1) crossover visit (day 30) and final visit (day 60) | 
| 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. | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | 
| 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. | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | 
| 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. | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | 
| 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. | basal visit (day 1), Crossover visit (day 30) and final visit (day 60) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Latanoprost, Glaucoma, Ocular hypertension, Crossover study