Study of Fixed-Dose Combinations of Trabodenoson and Latanoprost in Adults With OHT or POAG

Study Overview
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Brief Summary
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Phase II, randomized, double-masked study to evaluate the efficacy and tolerability of topical ocular delivery of fixed-dosed combinations of trabodenoson and latanoprost in subjects with Ocular Hypertension or Primary Open-Angle Glaucoma. All subjects who meet the study's enrollment criteria following Screening will undergo washout of all prohibited medications (if washout is needed), including their routine glaucoma medications. During the Placebo Run-In Period, placebo is applied twice daily to both eyes in all subjects. During the Treatment Period, study drug is applied to both eyes for a total of 8 weeks. Each subject will be assigned 4 weeks of AM and 4 weeks of PM dosing in a masked manner. AM vs PM dosing is masked utilizing Placebo in addition to the active drug product. During the Treatment Period, study drug (Active and Placebo) eye drop applications will occur twice daily, in the morning and in the evening. The Treatment Period will be followed by an Observation Period of approximately 7 days wherein no study eye drops are instilled. The purpose of the study is to assess the overall benefit/risk profile of binocular topical application of different doses of trabodenoson (3.0% and 6.0%) when combined with latanoprost (0.005% or 0.0025%) one drop daily (QD) for 8 weeks.

Detailed Description
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This is a phase II, randomized, double-masked study to evaluate the efficacy and tolerability of topical ocular delivery of fixed-dose combinations of trabodenoson and latanoprost in subjects with OHT or POAG. The Primary Objective of this Trial is to evaluate the efficacy of different topical ocular doses of trabodenoson (3.0% and 6.0%) when added to latanoprost (0.005% or 0.0025%), one drop daily to both eyes over two consecutive 4 week periods. The Secondary Objective is to evaluate the tolerability and safety of different doses of trabodenoson (3.0% and 6.0%) when added to latanoprost (0.005% or 0.0025%), one drop daily to both eyes over two consecutive 4 week periods. the Hypotheses is that topical ocular co-administration of 3.0% or 6.0% trabodenoson plus latanoprost 0.0025% or 0.005% ophthalmic formulation will reduce IOP and be well-tolerated. All subjects who meet the study's enrollment criteria following Screening will undergo washout of all prohibited medications, including their routine glaucoma medications. During the Placebo Run-In Period, placebo (vehicle control matched to trabodenoson) is applied twice daily to both eyes in all subjects. During the Treatment Period, study drug is applied to both eyes for a total of 8 weeks. Each subject will be assigned 4 weeks of AM and 4 weeks of PM dosing in a manner that is masked to the patient. The Treatment Period will be followed by an Observation Period of approximately 7 days wherein no study eye drops are instilled. To mimic what is generally seen in clinical trials, the number of subjects with ocular hypertension as their diagnosis will be limited to approximately 30% of the total subjects enrolled. Additionally, so the trial mirrors the general population demographics (so as to improve generalizability of the results) the proportion of African American subjects will be approximately 25% or less but not less than 12% of the total subjects enrolled. The purpose of the study is to assess the efficacy, tolerability, and safety of binocular topical application of different doses of trabodenoson (3.0% and 6.0%) when added to latanoprost (0.005% or 0.0025%) one drop daily over two consecutive 4 week periods in subjects with POAG or OHT. Data collection will include efficacy (masked-IOPs), local (ophthalmic) and systemic tolerability and safety assessments

Official Title
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Phase II, Randomized, Double-masked, Active-controlled Study of Fixed-Dose Combinations of Trabodenoson and Latanoprost in Subjects With Ocular Hypertension or Primary Open-Angle Glaucoma

Conditions
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Primary Open-Angle Glaucoma (POAG), Ocular Hypertension (OHT)

Intervention / Treatment
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* Drug: trabodenoson 6.0% / latanoprost 0.005% QD
* Drug: trabodenoson 3.0% / latanoprost 0.005% QD
* Drug: trabodenoson 6.0% / latanoprost 0.0025% QD
* Drug: latanoprost 0.005% QD
* Drug: latanoprost 0.0025% QD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ocular hypertension (OHT) or primary open-angle glaucoma (POAG) Mean Intraocular pressure (IOP) of ≥25 and ≤34 Exclusion Criteria: Significant visual field loss or any new field loss within the past year Cup-to-disc ratio >0.8 Central corneal thickness <490 µm or >610 µm A recent (acute) or chronic medical condition that might obfuscate the Subject's study data

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: trabodenoson 6.0% /latanoprost 0.005% QD<br>trabodenoson 6.0% / latanoprost 0.005% QD FDC | Drug: trabodenoson 6.0% / latanoprost 0.005% QD<br>* Trabodenoson 6.0% / latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.<br>|
| Experimental: trabodenoson 3.0% /latanoprost 0.005% QD<br>trabodenoson 3.0% / latanoprost 0.005% QD FDC | Drug: trabodenoson 3.0% / latanoprost 0.005% QD<br>* Trabodenoson 3.0% / latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.<br>|
| Experimental: trabodenoson 6.0% /latanoprost 0.0025%QD<br>trabodenoson 6.0% /latanoprost 0.0025% QD FDC | Drug: trabodenoson 6.0% / latanoprost 0.0025% QD<br>* Trabodenoson 6.0% / latanoprost 0.0025% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.<br>|
| Active Comparator: latanoprost 0.005% QD<br>latanoprost 0.005% ophthalmic solution QD | Drug: latanoprost 0.005% QD<br>* Latanoprost 0.005% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.<br>|
| Active Comparator: latanoprost 0.0025% QD<br>latanoprost 0.0025% ophthalmic solution QD | Drug: latanoprost 0.0025% QD<br>* Latanoprost 0.0025% administered once per day in both eyes and placebo administered once per day in both eyes, for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Intraocular Pressure (IOP) | Daily change from diurnal baseline in IOP | Two Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glaucoma, primary open-angle glaucoma, ocular hypertension, adenosine agonist, eye drop, trabodenoson, trabecular meshwork