Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome

Thrombosis and Haemostasis

Volumn 111, Issue 6, 2014, Pages 1141-1152

  Goldstein, Sidney ^a   Bates, Eric R ^b   Bhatt, Deepak L ^c   Cao, Charlie ^d   Holmes, David ^e   Kupfer, Stuart ^d   Martinez, Felipe ^f   Spaeder, Jeffrey ^d   Weitz, Jeffrey I ^g   Ye, Zhan ^d   Zannad, Faiez ^h  

^a HENRY FORD HOSPITAL   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d TAKEDA PHARMACEUTICALS   (United States)

^e MAYO CLINIC   (United States)

^f UNIVERSIDAD NACIONAL DE CÓRDOBA   (Argentina)

^g MCMASTER UNIVERSITY   (Canada)

^h UNIVERSITÉ DE LORRAINE   (France)

Author keywords

Acute coronary syndrome; Oral factor Xa inhibitors; Thrombosis

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LETAXABAN; PLACEBO; THIENOPYRIDINE DERIVATIVE; 1-(1-(3-((6-CHLORONAPHTHALEN-2-YL)SULFONYL)-2-HYDROXYPROPANOYL)PIPERIDIN-4-YL)TETRAHYDROPYRIMIDIN-2(1H)-ONE; ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR 10A INHIBITOR; PYRIMIDINONE DERIVATIVE; SULFONE;

ACUTE CORONARY SYNDROME; ADULT; ARTICLE; BLEEDING; BLOOD CLOT LYSIS; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; HEART INFARCTION; HEART LEFT BUNDLE BRANCH BLOCK; HEART LEFT VENTRICLE EJECTION FRACTION; HEART MUSCLE ISCHEMIA; HUMAN; INCIDENCE; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MORNING DOSAGE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RISK FACTOR; AGED; BLOOD; CHEMICALLY INDUCED; CLINICAL TRIAL; DOUBLE BLIND PROCEDURE; DRUG ADMINISTRATION; MULTICENTER STUDY; ORAL DRUG ADMINISTRATION; TREATMENT OUTCOME; VERY ELDERLY;

ACUTE CORONARY SYNDROME; ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; ANTICOAGULANTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FACTOR XA INHIBITORS; FEMALE; HEMORRHAGE; HUMANS; MALE; MIDDLE AGED; PYRIMIDINONES; SULFONES; TREATMENT OUTCOME;

EID: 84901916638     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH13-07-0543     Document Type: Article

References (21)

1. Rothberg MB, Celestin C, Fiore LD, et al. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 2005; 143: 241-250.
2. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494-502.
3. Mehta SR, Yusuf S, Peters RJG, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527-533.
4. Tomasello SD, Tello-Montoliu A, Angiolillo DJ. Prasugrel for the treatment of coronary thrombosis: a review of pharmacological properties, indications for use and future development. Expert Opin Investig Drugs 2011; 20: 119-133.
5. Andreotti F, Testa L, Biondi-Zoccai GGL, et al. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25 307 patients. Eur Heart J 2006; 27: 519-526.
6. van Es RF, Jonker JJ, Verheugt FW, et al. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 2002; 360: 109-113.
7. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347: 969-974.
8. APPRAISE Steering Committee and Investigators. Apixaban, an oral, direct, selective, factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome. Circulation 2009; 119: 2877-2885.
9. Mega JL, Braunwald E, Mohanavelu S, et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet 2009; 374: 29-38.
10. Alexander JH, Lopes RD, James S, et al, for the APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011; 365: 699-708.
11. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366: 9-19.
12. Fujimoto T, Imaeda Y, Konishi N, et al. Discovery of a tetrahydropyrimidin-2(1H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor. J Med Chem 2010 May 13; 53: 3517-3531.
13. Kawamura M, Konishi N, Hiroe K, et al. Antithrombotic and anticoagulant profiles of TAK-442, a novel factor Xa inhibitor, in a rabbit model of venous thrombosis. J Cardiovasc Pharmacol 2010; 56: 156-161.
14. Konishi N, Hiroe K, Kawamura M. Synergistic effect of factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats. Thromb Res 2010; 126: 124-129.
15. Stringer F, Scott G, Kupfer S, et al. The pharmacokinetics and pharmacodynamics of TAK-442, an oral, direct factor Xa inhibitor following multiple dosing in healthy male subjects. Br J Clin Pharmacol 2010; 70: 305 (Abstract).
16. Weitz JI, Cao C, Eriksson BI, et al. A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery. Thromb Haemost 2010; 104: 1150-1157.
17. Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987; 76: 142-154.
18. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
19. Buresly K, Eisenberg MJ, Zhang X, et al. Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med 2005; 165: 784-789.
20. Hermosillo J, Spinler SA. Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too dangerous? Ann Pharmacother 2008; 42: 790-805.
21. Steg PG, Mehta SR, Jukema W, et al. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome. Eur Heart J 2011; 32: 2541-2554.