Absence of QTc prolongation with betrixaban: A randomized, double-blind, placebo-and positive-controlled thorough ECG study

Expert Opinion on Pharmacotherapy

Volumn 14, Issue 1, 2013, Pages 5-13

  Morganroth, Joel ^a   Gretler, Daniel D ^b   Hollenbach, Stanley J ^b   Lambing, Joseph L ^b   Sinha, Uma ^b  

^a EResearch Technology Inc   (United States)

^b Portola Pharmaceuticals Inc   (United States)

Author keywords

Antithrombotic agent; Betrixaban; Coagulation factor Xa; ICH E14 guidance; QTcI interval

Indexed keywords

BETRIXABAN; MOXIFLOXACIN; PLACEBO;

AREA UNDER THE CURVE; ARTICLE; CONTACT DERMATITIS; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG SAFETY; DRUG TOLERABILITY; ELECTROCARDIOGRAM; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; QRS COMPLEX; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; ANTI-BACTERIAL AGENTS; ANTICOAGULANTS; AZA COMPOUNDS; BENZAMIDES; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; ELECTROCARDIOGRAPHY; FEMALE; HEART RATE; HUMANS; LONG QT SYNDROME; MALE; MIDDLE AGED; PYRIDINES; QUINOLINES; YOUNG ADULT;

EID: 84871563191     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2013.753057     Document Type: Article

References (15)

1. Sinha U, Delaney SM, Nanda N, et al. Antithrombotic activity of PRT54021, a potent oral direct factor Xa inhibitor, can be monitored using a novel prothrombinase inhibition bioassay [abstract 907]. Blood 2006;108:11
2. Abe K, Siu G, Edwards ST, et al. Animal models of thrombosis help predict the human therapeutic concentration of PRT54021, a potent oral factor Xa inhibitor [abstract 901]. Blood 2006;108:11
3. Cindy Xia. Absorption mechanism of MLN1021 in Caco-2 cells. Portola Pharmaceuticals, Inc; South San Francisco, CA: 2004; Data on file
4. Katzer D, Eggen M, Kollipara SA. An open-label, single-dose, mass-balance study to assess the disposition of 14C-labeled PRT054021 in healthy male subjects. Portola Pharmaceuticals, Inc; South San Francisco, CA: 2007; Data on file
5. Turpie AGG, Bauer KA, Davidson BL, et al. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost 2009;101(1):68-76
6. Ezekowitz M, Diaz R, Dorian P, et al. Randomized Clinical Trial of Three Doses of a Long-Acting Oral Direct Factor Xa Inhibitor Betrixaban in Patients with Atrial Fibrillation [abstract]. 59th Annual Meeting of the American Academy of Cardiology; 13-16 March 2010; Atlanta (GA
7. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry: E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. October 2005. Issued by the Approved by the International Conference on Harmonisation. Available from: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ ucm129357.pdf
8. Woosley RL, Chen Y, Freiman JP, et al. Mechanisms of the cardiotoxic actions of terfenadine. JAMA 1993;268(12):1532-6
9. Morganroth J. A definitive or thorough phase 1 QT ECG trial as a requirement for drug safety assessment. J Electrocardiol 2004;37(1):25-9 (Pubitemid 38168826)
10. Gupta A, Lawrence AT, Krishnan K, et al. Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes. Am Heart J 2007;153(6):891-9 (Pubitemid 46809861)
11. Bloomfield DM, Kost JT, Ghosh K, et al. The effect of moxifloxacin on QTc and implications for the design of thorough QT studies. Clin Pharmacol Ther 2008;84(4):679-3
12. Demolis JL, Kubitza D, Tenneze L, et al. Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects. Clin Pharmacol Ther 2000;68(6):658-66 (Pubitemid 32059992)
13. Malik M, Farbom P, Batchvarov V, et al. Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval. Heart 2002;87(3):220-8 (Pubitemid 34177674)
14. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart 1920;7:353-69
15. Fridericia LS. The duration of systole in an electrocardiogram in normal humans and in patients with heart disease. Ann Noninvasive Electrocardiol 2003;8(4):343-51 (Pubitemid 38569971)