Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study

Richard C. Becker; David J. Moliterno; Lisa K. Jennings; Karen S. Pieper; Jinglan Pei; Alan Niederman; Khaled M. Ziada; Gail Berman; John Strony; Diane Joseph; Kenneth W. Mahaffey; Frans Van de Werf; Enrico Veltri; Robert A. Harrington

doi:10.1016/S0140-6736(09)60230-0

Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study

Richard C. Becker, David J. Moliterno, Lisa K. Jennings, Karen S. Pieper, Jinglan Pei, Alan Niederman, Khaled M. Ziada, Gail Berman, John Strony, Diane Joseph, Kenneth W. Mahaffey, Frans Van de Werf, Enrico Veltri, Robert A. Harrington

Research output: Contribution to journal › Article › peer-review

304 Scopus citations

Abstract

Background: An antithrombotic drug is needed that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We therefore assessed the tolerability and safety of SCH 530348-an oral platelet protease-activated receptor-1 antagonist. Methods: We randomly assigned patients aged 45 years or older and undergoing non-urgent PCI or coronary angiography with planned PCI to an oral loading dose of SCH 530348 (10 mg, 20 mg, or 40 mg) or matching placebo in a 3:1 ratio in a multicentre international study. Those in the SCH 530348 group who subsequently underwent PCI (primary PCI cohort) continued taking an oral maintenance dose (0·5 mg, 1·0 mg, or 2·5 mg per day), and patients in the placebo group continued placebo for 60 days. The primary endpoint was the incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction (TIMI) scale. Both investigators and patients were unaware of treatment allocation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00132912. Findings: 257 patients were assigned to placebo and 773 to SCH 530348. The primary endpoint occurred in 2 (2%) of 129, 3 (3%) of 120, and 7 (4%) of 173 patients, respectively, in the SCH 530348 10 mg, 20 mg, and 40 mg groups compared with 5 (3%) of 151 patients in the placebo group (p=0·5786). TIMI major plus minor bleeding occurred in 3 (2%) of 136, 5 (4%) of 139, and 4 (3%) of 138 patients given SCH 530348 0·5 mg, 1·0 mg, and 2·5 mg once per day, respectively (p=0·7561). Interpretation: Oral SCH 530348 was generally well tolerated and did not cause increased TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel. Further testing in phase III trials to accurately define the safety and efficacy of SCH 530348 is warranted. Funding: Schering-Plough Research Institute.

Original language	English
Pages (from-to)	919-928
Number of pages	10
Journal	The Lancet
Volume	373
Issue number	9667
DOIs	https://doi.org/10.1016/S0140-6736(09)60230-0
State	Published - 2009

Bibliographical note

Funding Information:
RCB receives research funding from Schering-Plough. DJM has received honoraria and consulting fees from Schering-Plough. LKJ is on the advisory board, and receives research funding and honoraria from Schering-Plough. JP, GB, JS, and EV are employees of Schering-Plough. EV owns stock and stock options in Schering-Plough. KWM receives research funding and consulting fees from Schering-Plough. FVDW has received research funding, honoraria for speaker's bureau and participating on an advisory board for Schering-Plough. RAH receives research funding and consulting fees from Schering-Plough. KP, AN, KMZ, and DJ declare that they have no conflict of interest.

Funding Information:
TRA-PCI was sponsored by Schering-Plough Research Institute. We thank Eric Reyes of North Carolina State University for statistical assistance, and Amanda McMillan of the DCRI for her editorial assistance.

Funding

RCB receives research funding from Schering-Plough. DJM has received honoraria and consulting fees from Schering-Plough. LKJ is on the advisory board, and receives research funding and honoraria from Schering-Plough. JP, GB, JS, and EV are employees of Schering-Plough. EV owns stock and stock options in Schering-Plough. KWM receives research funding and consulting fees from Schering-Plough. FVDW has received research funding, honoraria for speaker's bureau and participating on an advisory board for Schering-Plough. RAH receives research funding and consulting fees from Schering-Plough. KP, AN, KMZ, and DJ declare that they have no conflict of interest. TRA-PCI was sponsored by Schering-Plough Research Institute. We thank Eric Reyes of North Carolina State University for statistical assistance, and Amanda McMillan of the DCRI for her editorial assistance.

Funders	Funder number
Schering-Plough Research Institute
Schering Plough Co

ASJC Scopus subject areas

General Medicine

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10.1016/S0140-6736(09)60230-0

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Becker, R. C., Moliterno, D. J., Jennings, L. K., Pieper, K. S., Pei, J., Niederman, A., Ziada, K. M., Berman, G., Strony, J., Joseph, D., Mahaffey, K. W., Van de Werf, F., Veltri, E., & Harrington, R. A. (2009). Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study. The Lancet, 373(9667), 919-928. https://doi.org/10.1016/S0140-6736(09)60230-0

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title = "Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study",

abstract = "Background: An antithrombotic drug is needed that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We therefore assessed the tolerability and safety of SCH 530348-an oral platelet protease-activated receptor-1 antagonist. Methods: We randomly assigned patients aged 45 years or older and undergoing non-urgent PCI or coronary angiography with planned PCI to an oral loading dose of SCH 530348 (10 mg, 20 mg, or 40 mg) or matching placebo in a 3:1 ratio in a multicentre international study. Those in the SCH 530348 group who subsequently underwent PCI (primary PCI cohort) continued taking an oral maintenance dose (0·5 mg, 1·0 mg, or 2·5 mg per day), and patients in the placebo group continued placebo for 60 days. The primary endpoint was the incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction (TIMI) scale. Both investigators and patients were unaware of treatment allocation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00132912. Findings: 257 patients were assigned to placebo and 773 to SCH 530348. The primary endpoint occurred in 2 (2%) of 129, 3 (3%) of 120, and 7 (4%) of 173 patients, respectively, in the SCH 530348 10 mg, 20 mg, and 40 mg groups compared with 5 (3%) of 151 patients in the placebo group (p=0·5786). TIMI major plus minor bleeding occurred in 3 (2%) of 136, 5 (4%) of 139, and 4 (3%) of 138 patients given SCH 530348 0·5 mg, 1·0 mg, and 2·5 mg once per day, respectively (p=0·7561). Interpretation: Oral SCH 530348 was generally well tolerated and did not cause increased TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel. Further testing in phase III trials to accurately define the safety and efficacy of SCH 530348 is warranted. Funding: Schering-Plough Research Institute.",

author = "Becker, {Richard C.} and Moliterno, {David J.} and Jennings, {Lisa K.} and Pieper, {Karen S.} and Jinglan Pei and Alan Niederman and Ziada, {Khaled M.} and Gail Berman and John Strony and Diane Joseph and Mahaffey, {Kenneth W.} and {Van de Werf}, Frans and Enrico Veltri and Harrington, {Robert A.}",

note = "Funding Information: RCB receives research funding from Schering-Plough. DJM has received honoraria and consulting fees from Schering-Plough. LKJ is on the advisory board, and receives research funding and honoraria from Schering-Plough. JP, GB, JS, and EV are employees of Schering-Plough. EV owns stock and stock options in Schering-Plough. KWM receives research funding and consulting fees from Schering-Plough. FVDW has received research funding, honoraria for speaker's bureau and participating on an advisory board for Schering-Plough. RAH receives research funding and consulting fees from Schering-Plough. KP, AN, KMZ, and DJ declare that they have no conflict of interest. Funding Information: TRA-PCI was sponsored by Schering-Plough Research Institute. We thank Eric Reyes of North Carolina State University for statistical assistance, and Amanda McMillan of the DCRI for her editorial assistance. ",

year = "2009",

doi = "10.1016/S0140-6736(09)60230-0",

language = "English",

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Becker, RC, Moliterno, DJ, Jennings, LK, Pieper, KS, Pei, J, Niederman, A, Ziada, KM, Berman, G, Strony, J, Joseph, D, Mahaffey, KW, Van de Werf, F, Veltri, E & Harrington, RA 2009, 'Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study', The Lancet, vol. 373, no. 9667, pp. 919-928. https://doi.org/10.1016/S0140-6736(09)60230-0

TY - JOUR

T1 - Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention

T2 - a randomised, double-blind, placebo-controlled phase II study

AU - Becker, Richard C.

AU - Moliterno, David J.

AU - Jennings, Lisa K.

AU - Pieper, Karen S.

AU - Pei, Jinglan

AU - Niederman, Alan

AU - Ziada, Khaled M.

AU - Berman, Gail

AU - Strony, John

AU - Joseph, Diane

AU - Mahaffey, Kenneth W.

AU - Van de Werf, Frans

AU - Veltri, Enrico

AU - Harrington, Robert A.

N1 - Funding Information: RCB receives research funding from Schering-Plough. DJM has received honoraria and consulting fees from Schering-Plough. LKJ is on the advisory board, and receives research funding and honoraria from Schering-Plough. JP, GB, JS, and EV are employees of Schering-Plough. EV owns stock and stock options in Schering-Plough. KWM receives research funding and consulting fees from Schering-Plough. FVDW has received research funding, honoraria for speaker's bureau and participating on an advisory board for Schering-Plough. RAH receives research funding and consulting fees from Schering-Plough. KP, AN, KMZ, and DJ declare that they have no conflict of interest. Funding Information: TRA-PCI was sponsored by Schering-Plough Research Institute. We thank Eric Reyes of North Carolina State University for statistical assistance, and Amanda McMillan of the DCRI for her editorial assistance.

PY - 2009

Y1 - 2009

N2 - Background: An antithrombotic drug is needed that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We therefore assessed the tolerability and safety of SCH 530348-an oral platelet protease-activated receptor-1 antagonist. Methods: We randomly assigned patients aged 45 years or older and undergoing non-urgent PCI or coronary angiography with planned PCI to an oral loading dose of SCH 530348 (10 mg, 20 mg, or 40 mg) or matching placebo in a 3:1 ratio in a multicentre international study. Those in the SCH 530348 group who subsequently underwent PCI (primary PCI cohort) continued taking an oral maintenance dose (0·5 mg, 1·0 mg, or 2·5 mg per day), and patients in the placebo group continued placebo for 60 days. The primary endpoint was the incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction (TIMI) scale. Both investigators and patients were unaware of treatment allocation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00132912. Findings: 257 patients were assigned to placebo and 773 to SCH 530348. The primary endpoint occurred in 2 (2%) of 129, 3 (3%) of 120, and 7 (4%) of 173 patients, respectively, in the SCH 530348 10 mg, 20 mg, and 40 mg groups compared with 5 (3%) of 151 patients in the placebo group (p=0·5786). TIMI major plus minor bleeding occurred in 3 (2%) of 136, 5 (4%) of 139, and 4 (3%) of 138 patients given SCH 530348 0·5 mg, 1·0 mg, and 2·5 mg once per day, respectively (p=0·7561). Interpretation: Oral SCH 530348 was generally well tolerated and did not cause increased TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel. Further testing in phase III trials to accurately define the safety and efficacy of SCH 530348 is warranted. Funding: Schering-Plough Research Institute.

AB - Background: An antithrombotic drug is needed that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We therefore assessed the tolerability and safety of SCH 530348-an oral platelet protease-activated receptor-1 antagonist. Methods: We randomly assigned patients aged 45 years or older and undergoing non-urgent PCI or coronary angiography with planned PCI to an oral loading dose of SCH 530348 (10 mg, 20 mg, or 40 mg) or matching placebo in a 3:1 ratio in a multicentre international study. Those in the SCH 530348 group who subsequently underwent PCI (primary PCI cohort) continued taking an oral maintenance dose (0·5 mg, 1·0 mg, or 2·5 mg per day), and patients in the placebo group continued placebo for 60 days. The primary endpoint was the incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction (TIMI) scale. Both investigators and patients were unaware of treatment allocation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00132912. Findings: 257 patients were assigned to placebo and 773 to SCH 530348. The primary endpoint occurred in 2 (2%) of 129, 3 (3%) of 120, and 7 (4%) of 173 patients, respectively, in the SCH 530348 10 mg, 20 mg, and 40 mg groups compared with 5 (3%) of 151 patients in the placebo group (p=0·5786). TIMI major plus minor bleeding occurred in 3 (2%) of 136, 5 (4%) of 139, and 4 (3%) of 138 patients given SCH 530348 0·5 mg, 1·0 mg, and 2·5 mg once per day, respectively (p=0·7561). Interpretation: Oral SCH 530348 was generally well tolerated and did not cause increased TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel. Further testing in phase III trials to accurately define the safety and efficacy of SCH 530348 is warranted. Funding: Schering-Plough Research Institute.

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Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study

Abstract

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