Trial Outcomes & Findings for Trial to Assess the Ocular Safety of Vorapaxar (SCH 530348) in Participants With Atherosclerosis (Study P05183) (NCT NCT00617123)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

258 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2018-09-21

Participant Flow

Participants were recruited from participants enrolled in Study SCH 530348 P04737 (NCT00526474) and met the inclusion/exclusion criteria for this study.

A total of 258 particpants were referred to opthalmology sites, 65 of whom did not particpate in this study (P05138) beyond the screening visit and were not included in the analysis of ocular safety. A total of 193 participants were included in the analysis of ocular safety.

Participant milestones

Participant milestones
Measure	Vorapaxar Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year
Referral Screening Period STARTED	137	121
Referral Screening Period COMPLETED	98	95
Referral Screening Period NOT COMPLETED	39	26
Study Treatment Period STARTED	98	95
Study Treatment Period Treated	97	95
Study Treatment Period COMPLETED	81	79
Study Treatment Period NOT COMPLETED	17	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Vorapaxar Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year
Referral Screening Period Did Not Meet Protocol Eligibility	36	24
Referral Screening Period Did Not Wish To Continue	3	1
Referral Screening Period Adverse Event	0	1
Study Treatment Period Withdrawal by Subject	8	12
Study Treatment Period Adverse Event	7	3
Study Treatment Period Did Not Meet Protocol Eligibility	2	0
Study Treatment Period Noncompliance with Protocol	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vorapaxar n=98 Participants Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo n=95 Participants Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year	Total n=193 Participants Total of all reporting groups
Age, Continuous	56.6 years STANDARD_DEVIATION 10.1 • n=5 Participants	55.3 years STANDARD_DEVIATION 11.7 • n=7 Participants	55.9 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	26 Participants n=7 Participants	53 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	69 Participants n=7 Participants	140 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: The analysis population consisted of all participants who took at least one dose of study medication, and had a baseline and at least one post-baseline vacuolation assessment.

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).

Outcome measures

Outcome measures
Measure	Vorapaxar n=91 Participants Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo n=86 Participants Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year
Number of Participants Who Develop Vacuolization in the Inner Nuclear Layer (INL) of the Retina as Measured by Ocular Coherence Tomography (OCT) 4 months (n=91, n=86)	1 participants	0 participants
Number of Participants Who Develop Vacuolization in the Inner Nuclear Layer (INL) of the Retina as Measured by Ocular Coherence Tomography (OCT) 8 months (n=86, n=80)	1 participants	0 participants
Number of Participants Who Develop Vacuolization in the Inner Nuclear Layer (INL) of the Retina as Measured by Ocular Coherence Tomography (OCT) 12 months (n=77, n=78)	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and 4, 8 and 12 months

Population: The analysis population consisted of all participants who took at least one dose of study medication, and had a baseline and at least one post-baseline visual acuity score.

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.

Outcome measures

Outcome measures
Measure	Vorapaxar n=90 Participants Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo n=86 Participants Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year
Number of Participants Who Have a Decrease in Visual Acuity Score of at Least Seven Letters From Baseline 4 months (n=90, n=86)	10 participants	8 participants
Number of Participants Who Have a Decrease in Visual Acuity Score of at Least Seven Letters From Baseline 8 months (n=86, n=80)	10 participants	8 participants
Number of Participants Who Have a Decrease in Visual Acuity Score of at Least Seven Letters From Baseline 12 months (n=78, n=78)	7 participants	9 participants

SECONDARY outcome

Timeframe: Baseline and 4, 8 and 12 months

Population: The analysis population consisted of all participants who took at least one dose of study medication, and had a baseline and at least one post-baseline center point thickness assessment 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.

Outcome measures

Outcome measures
Measure	Vorapaxar n=91 Participants Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo n=86 Participants Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year
Number of Participants With Change From Baseline of Center Foveal Thickness of Greater Than 15 Microns as Measured by OCT 4 months (n=91, n=86)	27 participants	28 participants
Number of Participants With Change From Baseline of Center Foveal Thickness of Greater Than 15 Microns as Measured by OCT 8 months (n=86, n=80)	23 participants	26 participants
Number of Participants With Change From Baseline of Center Foveal Thickness of Greater Than 15 Microns as Measured by OCT 12 months (n=77, n=78)	19 participants	29 participants

SECONDARY outcome

Timeframe: Baseline and 4, 8 and 12 months

Population: The analysis population consisted of all participants who took at least one dose of study medication, and had a baseline and at least one post-baseline numerical score of graded abnormalities assessment 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.

Outcome measures

Outcome measures
Measure	Vorapaxar n=92 Participants Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo n=87 Participants Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by OCT Baseline score (n=92, n=87)	3.1 score on a scale Standard Error 0.3	3.4 score on a scale Standard Error 0.4
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by OCT 4 months change (n=91, n=86)	0.2 score on a scale Standard Error 0.3	0.7 score on a scale Standard Error 0.3
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by OCT 8 months change (n=86, n=80)	0.6 score on a scale Standard Error 0.3	0.9 score on a scale Standard Error 0.3
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by OCT 12 months change (n=77, n=78)	0.2 score on a scale Standard Error 0.3	0.0 score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline and 4, 8 and 12 months

Population: The analysis population consisted of all participants who took at least one dose of study medication, and had a baseline and at least one post-baseline numerical score of graded abnormalities assessment as measured by fundus photogrpahy.

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.

Outcome measures

Outcome measures
Measure	Vorapaxar n=91 Participants Participants receive a vorapaxar 2.5 mg tablet administered orally once daily for 1 year	Placebo n=87 Participants Participants receive a matching placebo tablet to vorapaxar administered orally once daily for 1 year
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by Fundus Photography 8 months change (n=86, n=80)	-0.4 score on a scale Standard Error 0.4	-0.6 score on a scale Standard Error 0.4
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by Fundus Photography Baseline score (n=91, n=87)	4.1 score on a scale Standard Error 0.4	3.9 score on a scale Standard Error 0.4
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by Fundus Photography 4 months change (n=90, n=86)	-0.2 score on a scale Standard Error 0.4	-0.4 score on a scale Standard Error 0.3
Change From Baseline in the Numerical Score of Graded Abnormalities as Measured by Fundus Photography 12 months change (n=76, n=77)	-0.6 score on a scale Standard Error 0.5	-0.3 score on a scale Standard Error 0.5

Adverse Events

Vorapaxar

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.
Publication restrictions are in place

Restriction type: OTHER