Trial to Assess the Ocular Safety of Vorapaxar (SCH 530348) in Participants With Atherosclerosis (Study P05183)

Study Overview
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Brief Summary
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This study is designed to evaluate the long-term ocular safety of SCH 530348 (vorapaxar) in participants with established atherosclerotic disease who are enrolled into the TRA 2°P - TIMI 50 Study (P04737) (NCT00526474).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Ocular Safety of SCH 530348 in Subjects Participating in the Schering-Plough P04737 Study (TRA^SM-Secondary Prevention Ocular Safety Study)

Conditions
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Atherosclerosis, Ischemia, Myocardial Infarction, Cerebrovascular Accident

Intervention / Treatment
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* Drug: Vorapaxar 2.5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence or a history of atherosclerosis involving the coronary, cerebral, or peripheral vascular systems Exclusion Criteria: The study will include participants who meet none of the exclusion criteria for the parent protocol (P04737) and also the following: history or evidence of age-related macular degeneration on baseline evaluation history of diabetic macular edema, or evidence of treated diabetic retinopathy on baseline evaluation history or evidence of other retinal diseases, including retinal injury, on baseline evaluation history or evidence of retinal surgery, including laser photocoagulation, on baseline evaluation history or evidence of glaucoma on baseline evaluation history or evidence of high intraocular pressure of >22 mm Hg on baseline evaluation evidence of center foveal thickness of >190 µm on baseline OCT examination presence of vacuoles in the retina on baseline OCT

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vorapaxar<br>Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year | Drug: Vorapaxar 2.5 mg<br>* Vorapaxar 2.5 mg oral tablet<br>|
| Placebo Comparator: Placebo<br>Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year | Drug: Placebo<br>* matching placebo oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Develop Vacuolization in the Inner Nuclear Layer (INL) of the Retina as Measured by Ocular Coherence Tomography (OCT) | Vacuolization is defined as the presence of more than one vacuole (defined as a clear, round structure in the INL of the retina of at least 30 microns in diameter) compared to baseline in either the left or right eye as evaluated by ocular coherence tomography (OCT). | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Have a Decrease in Visual Acuity Score of at Least Seven Letters From Baseline | Visual acuity was assessed in both eyes by best corrected visual acuity following standardized refraction. The best corrected visual acuity score is the number of letters on a standard visual acuity testing chart read correctly by a participant. A decrease in best corrected visual acuity score in the left and/or right eye indicates a worsening of vision. | Baseline and 4, 8 and 12 months | 
| Number of Participants With Change From Baseline of Center Foveal Thickness of Greater Than 15 Microns as Measured by OCT | Center foveal thickness measured by OCT was evaluated for a change from baseline in greater than 15 microns in either the left or right eye. | Baseline and 4, 8 and 12 months | 
| Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by OCT | Individual OCT abnormalities were scored as 0=not present or 1=present. The total number of possible abnormalities present was 84 (42 possible abnormalities per eye). Data are for the left and right eyes combined (score range: 0 to 84). Change from Baseline at a given timepoint was calculated as Timepoint Score minus Baseline Score. A smaller score indicates fewer graded abnormalities. | Baseline and 4, 8 and 12 months | 
| Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by Fundus Photography | Individual fundus photography abnormalities were scored as 0=not present or 1=present. The total number of possible abnormalities present was 48 (24 possible abnomalities per eye). Data are for the left and right eyes combined (score range: 0 to 48). Change from Baseline at a given timepoint was calculated as Timepoint Score minus Baseline Score. A smaller score indicates fewer graded abnormalities. | Baseline and 4, 8 and 12 months |