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


RESULTS
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).


CONCLUSIONS
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.
Becker
Richard C
RC
Duke Clinical Research Institute, Durham, NC, USA.
Moliterno
David J
DJ
Jennings
Lisa K
LK
Pieper
Karen S
KS
Pei
Jinglan
J
Niederman
Alan
A
Ziada
Khaled M
KM
Berman
Gail
G
Strony
John
J
Joseph
Diane
D
Mahaffey
Kenneth W
KW
Van de Werf
Frans
F
Veltri
Enrico
E
Harrington
Robert A
RA
D015906:Angioplasty, Balloon, Coronary; D003327:Coronary Disease / Q000401:mortality / Q000628:therapy*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007783:Lactones / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*
D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D018179:Receptors, Thrombin; C530299:vorapaxar