Assessing the probability of drug-induced QTc-interval prolongation during clinical drug development

Clinical Pharmacology and Therapeutics

Volumn 90, Issue 6, 2011, Pages 867-875

  Chain, A S Y ^a   Krudys, K M ^b   Danhof, M ^a   Della Pasqua, O ^a,b  

^a LEIDEN UNIVERSITY   (Netherlands)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GREPAFLOXACIN; MOXIFLOXACIN; SOTALOL;

ARTICLE; BAYES THEOREM; CIRCADIAN RHYTHM; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG INDUCED DISEASE; HEART RATE; HUMAN; MAXIMUM PLASMA CONCENTRATION; PHARMACODYNAMICS; PRIORITY JOURNAL; PROBABILITY; QT INTERVAL; QT PROLONGATION; RISK ASSESSMENT; SINGLE DRUG DOSE;

ADOLESCENT; ADULT; BAYES THEOREM; CIRCADIAN RHYTHM; CLINICAL TRIALS AS TOPIC; DRUG AND NARCOTIC CONTROL; DRUG DESIGN; FEMALE; GUIDELINES AS TOPIC; HEART RATE; HUMANS; LONG QT SYNDROME; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS; YOUNG ADULT;

EID: 81355123270     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2011.202     Document Type: Article

References (40)

1. Guidance for Industry: ICH E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrythmic Potential for Non-Antiarrythmic Drugs. U.S. Department of Health and Human Services. Food and Drug Administration. (2005) 〈http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129357. pdf〉.
2. Darpo, B., Nebout, T. & Sager, P.T. Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline. J. Clin. Pharmacol. 46, 498-507 (2006).
3. Hutmacher, M.M., Chapel, S., Agin, M.A., Fleishaker, J.C. & Lalonde, R.L. Performance characteristics for some typical QT study designs under the ICH E-14 guidance. J. Clin. Pharmacol. 48, 215-224 (2008).
4. Pollard, C.E., Valentin, J.P. & Hammond, T.G. Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective. Br. J. Pharmacol. 154, 1538-1543 (2008).
5. Zareba, W. Drug induced QT prolongation. Cardiol. J. 14, 523-533 (2007). (Pubitemid 351278615)
6. Interdisciplinary Review Team for QT Studies. Manual of policies and procedures MAPP 6020.14. Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (2007). 〈http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ ManualofPoliciesProcedures/ucm082015.pdf〉.
7. Tsong, Y., Shen, M., Zhong, J. & Zhang, J. Statistical issues of QT prolongation assessment based on linear concentration modeling. J. Biopharm. Stat. 18, 564-584 (2008). (Pubitemid 351891695)
8. Boos, D.D., Hoffman, D., Kringle, R. & Zhang, J. New confidence bounds for QT studies. Stat. Med. 26, 3801-3817 (2007). (Pubitemid 47307750)
9. Garnett, C.E. et al. Concentration-QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review. J. Clin. Pharmacol. 48, 13-18 (2008). (Pubitemid 350292272)
10. Bloomfield, D. & Krishna, R. Commentary on the clinical relevance of concentration/QTc relationships for new drug candidates. J. Clin. Pharmacol. 48, 6-8 (2008). (Pubitemid 350292270)
11. Malik, M. et al. Thorough QT/QTc study in patients with advanced Parkinson's disease: cardiac safety of rotigotine. Clin. Pharmacol. Ther. 84, 595-603 (2008).
12. Malik, M., Hnatkova, K., Ford, J. & Madge, D. Near-thorough QT study as part of a first-in-man study. J. Clin. Pharmacol. 48, 1146-1157 (2008).
13. Rohatagi, S., Carrothers, T.J., Kuwabara-Wagg, J. & Khariton, T. Is a thorough QTc study necessary? The role of modeling and simulation in evaluating the QTc prolongation potential of drugs. J. Clin. Pharmacol. 49, 1284-1296 (2009).
14. Vandemeulebroecke, M., Lembcke, J., Wiesinger, H., Sittner, W. & Lindemann, S. Assessment of QT(c)-prolonging potential of BX471 in healthy volunteers. A 'thorough QT study' following ICH E14 using various QT(c) correction methods. Br. J. Clin. Pharmacol. 68, 435-446 (2009).
15. Pater, C. Methodological considerations in the design of trials for safety assessment of new drugs and chemical entities. Curr. Control Trials Cardiovasc. Med. 6, 1 (2005).
16. Anand, S.P. & Ghosh, S.K. A Bayesian approach for investigating the risk of QT prolongation .J Stat Theory Pract. 3, 445-454 (2009).
17. Kathman, S.J., Williams, D.H., Hodge, J.P. & Dar, M. A Bayesian population PKPD model of ispinesib-induced myelosuppression. Clin. Pharmacol. Ther. 81, 88-94 (2007). (Pubitemid 46050871)
18. Wheeler, W. Evolution of the thorough QT/QTc study. Regulatory Rapporteur 7 (11), 21-23 (2010).
19. Shah, R.R. Drug-induced prolongation of the QT interval: regulatory dilemmas and implications for approval and labelling of a new chemical entity. Fundam. Clin. Pharmacol. 16, 147-156 (2002). (Pubitemid 34587799)
20. Chapel, S., Hutmacher, M.M., Bockbrader, H., de Greef, R. & Lalonde, R.L. Comparison of QTc data analysis methods recommended by the ICH E14 guidance and exposure-response analysis: case study of a thorough QT study of asenapine. Clin. Pharmacol. Ther. 89, 75-80 (2011).
21. Allen, M.J., Nichols, D.J. & Oliver, S.D. The pharmacokinetics and pharmacodynamics of oral dofetilide after twice daily and three times daily dosing. Br. J. Clin. Pharmacol. 50, 247-253 (2000).
22. Lin, Y.L., Chan, K. Pharmacokinetic and pharmacodynamic characterization of non-antiarrhythmic QT-prolonging drugs associated with torsade de pointes. Drug Inf. J. 42, 211-219 (2008). (Pubitemid 351775939)
23. Barbey, J.T., Sale, M.E., Woosley, R.L., Shi, J., Melikian, A.P. & Hinderling, P.H. Pharmacokinetic, pharmacodynamic, and safety evaluation of an accelerated dose titration regimen of sotalol in healthy middle-aged subjects. Clin. Pharmacol. Ther. 66, 91-99 (1999). (Pubitemid 29350450)
24. Jonker, D.M., Kenna, L.A., Leishman, D., Wallis, R., Milligan, P.A. & Jonsson, E.N. A pharmacokinetic-pharmacodynamic model for the quantitative prediction of dofetilide clinical QT prolongation from human ether-a-gogo-related gene current inhibition data. Clin. Pharmacol. Ther. 77, 572-582 (2005). (Pubitemid 40824970)
25. Schoemaker, R.C., van Gerven, J.M. & Cohen, A.F. Estimating potency for the Emax-model without attaining maximal effects. J. Pharmacokinet. Biopharm. 26, 581-593 (1998). (Pubitemid 29157784)
26. Dixon, R. et al. Lamotrigine does not prolong QTc in a thorough QT/QTc study in healthy subjects. Br. J. Clin. Pharmacol. 66, 396-404 (2008).
27. Bloomfield, D. M., Kost, J.T., Ghosh, K., Hreniuk, D., Hickey, L. A., Guitierrez, M. J. et al. The effect of moxifloxacin on QTc and implications for the design of thorough QT studies. Clin. Pharmacol. Ther. 84, 475-480 (2008).
28. Danhof, M., de Lange, E.C., Della Pasqua, O.E., Ploeger, B.A. & Voskuyl, R.A. Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling in translational drug research. Trends Pharmacol. Sci. 29, 186-191 (2008).
29. Beal, S. & Sheiner, L. NONMEM User's Guide (NONMEM Project Group: San Francisco, CA, 1999).
30. Bachman, W.J. & Gillespie, W.R. Truncated sigmoid Emax models: a reparameterization of the Sigmoid Emax model for use with truncated PK/PD data. Annual meeting of the American Society for Clinical Pharmacology and Therapeutics, New Orleans, LA, 30 March-1 April 1998.
31. Piotrovsky, V. Pharmacokinetic-pharmacodynamic modeling in the data analysis and interpretation of drug-induced QT/QTc prolongation. AAPS J. 7, E609-E624 (2005).
32. Spiegelhalter, D., Thomas, A., Best, N. & Gilks, W. BUGS: Bayesian Inference Using Gibbs Sampling, Version 1.4.1 (MRC Biostatistics Unit, Cambridge, UK, 2003).
33. Lunn, D.J., Thomas, A., Best, N. & Spiegelhalter, D. WinBUGS-A Bayesian modelling framework: concepts, structure, and extensibility. Stat Comput. 10, 325-337 (2000).
34. Lunn, D.J., Best, N., Thomas, A., Wakefield, J. & Spiegelhalter, D. Bayesian analysis of population PK/PD models: general concepts and software. J. Pharmacokinet. Pharmacodyn. 29, 271-307 (2002). (Pubitemid 35333143)
35. Duffull, S.B., Kirkpatrick, C.M., Green, B. & Holford, N.H. Analysis of population pharmacokinetic data using NONMEM and WinBUGS. J. Biopharm. Stat. 15, 53-73 (2005). (Pubitemid 40130000)
36. Spiegelhalter, D.A.K & Myles, J. Bayesian Approaches to Clinical Trials and Health Care Evaluations (Wiley: New York, 2004).
37. Spiegelhalter, D., Best, N. & Carlin, B. Bayesian measures of model complexity and fit. J. Roy. Stat. Soc. Ser. B 583-639 (2002).
38. Brooks, S.P. & Gelman, A. General methods for monitoring convergence of iterative simulations. J. Comput. Graph. Stat. 434-455 (1998). (Pubitemid 128635035)
39. Gelman, A.,Rubin, D. Inference from iterative simulation using multiple sequences. Stat. Sci. 7, 457-472 (1992).
40. Gelman, A., Carlin, J.B., Stern, H.S. & Rubin, D.B. Bayesian Data Analysis (Chapman & Hall: London, 2003).