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

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)

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).

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Ischemia; Atherosclerosis; Cerebrovascular Accident
• Intervention / Treatment: Drug: Placebo; Drug: Vorapaxar 2.5 mg

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Duke Clinical Research Institute; The TIMI (Thrombolysis in Myocardial Infarction) Study Group

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: February 4, 2008
• First Submitted That Met QC Criteria: February 4, 2008
• First Posted (Estimate): February 15, 2008

Study Record Updates

• Last Update Posted (Actual): September 21, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Myocardial Infarction; Infarction; Stroke; Ischemia; Atherosclerosis; Platelet Aggregation Inhibitors; Vorapaxar
• Other Study ID Numbers: P05183; MK-5348-018 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis