Drug-induced QT interval prolongation: Does ethnicity of the thorough QT study population matter?

British Journal of Clinical Pharmacology

Volumn 75, Issue 2, 2013, Pages 347-358

  Shah, Rashmi R ^a  

^a Rashmi Shah Consultancy Ltd   (United Kingdom)

Author keywords

Ethnicity; Exposure; Levofloxacin; Moxifloxacin; Quinidine; Response analysis; Thorough QT study

Indexed keywords

ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; ANALGESIC AGENT; ANESTHETIC AGENT; ANTIANGINA PECTORIS AGENT; ANTIARRHYTHMIC AGENT; ANTIDEPRESSANT AGENT; ANTIFUNGAL AGENT; ANTIHISTAMINIC AGENT; ANTIINFECTIVE AGENT; ANTILIPEMIC AGENT; ANTIMALARIAL AGENT; ANTITUSSIVE AGENT; CYTOTOXIC AGENT; NEUROLEPTIC AGENT; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; OPIATE AGONIST; PHOSPHODIESTERASE INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; PROTEINASE INHIBITOR; QUINOLINE DERIVED ANTIINFECTIVE AGENT; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SEROTONIN ANTAGONIST;

ARTICLE; CAUCASIAN; CLINICAL TRIAL (TOPIC); DRUG POTENCY; DRUG SURVEILLANCE PROGRAM; ETHNIC DIFFERENCE; HUMAN; MEDICAL INFORMATION SYSTEM; PHARMACOGENETICS; PRIORITY JOURNAL; QT INTERVAL; QT PROLONGATION;

CLINICAL TRIALS AS TOPIC; CONTINENTAL POPULATION GROUPS; DOSE-RESPONSE RELATIONSHIP, DRUG; ETHNIC GROUPS; HUMANS; LONG QT SYNDROME; PHARMACEUTICAL PREPARATIONS; PHARMACOGENETICS; RESEARCH SUBJECTS;

EID: 84872253299     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2012.04415.x     Document Type: Article

References (71)

1. International Conference on Harmonisation. The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals (ICH S7B). ICH, Geneva, 12 May 2005. Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S7B/Step4/S7B_Guideline.pdf [last accessed 26 January 2012].
2. International Conference on Harmonisation. The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-antiarrhythmic Drugs (ICH E14). ICH, Geneva, 12 May 2005. Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E14/E14_Guideline.pdf [last accessed 26 January 2012].
3. Milon D, Daubert JC, Saint-Marc C, Gouffault J. Torsade de pointes. Apropos of 54 cases. Ann Fr Anesth Reanim 1982; 1: 513-520.
4. Wysowski DK, Corken A, Gallo-Torres H, Talarico L, Rodriguez EM. Postmarketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and Food and Drug Administration regulatory actions. Am J Gastroenterol 2001; 96: 1698-1703.
5. Salle P, Rey JL, Bernasconi P, Quiret JC, Lombaert M. Torsades de pointe. Apropos of 60 cases. Ann Cardiol Angeiol (Paris) 1985; 34: 381-388.
6. Fung MC, Hsiao-hui Wu H, Kwong K, Hornbuckle K, Muniz E. Evaluation of the profile of patients with QTc prolongation in spontaneous adverse event reporting over the past three decades - 1969-98. Pharmacoepidemiol Drug Saf 2000; 9: (Suppl. 1): S24.
7. Faber TS, Zehender M, Just H. Drug-induced torsade de pointes. Incidence, management and prevention. Drug Saf 1994; 11: 463-476.
8. Shah RR. Drug-induced prolongation of the QT interval: regulatory dilemmas and implications for approval and labelling of a new chemical entity. Fundam Clin Pharmacol 2002; 16: 147-156.
9. Shah RR. Can pharmacogenetics help rescue drugs withdrawn from the market? Pharmacogenomics 2006; 7: 889-908.
10. Bertilsson L, Kalow W. Interethnic differences in drug disposition and effects. In: Interindividual Variability in Human Drug Metabolism, ed. Pacifici GM. Pelkonen O, London: Taylor & Francis, 2001; 15-74.
11. Xie HG, Kim RB, Wood AJ, Stein CM. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol 2001; 41: 815-850.
12. Shah RR. Pharmacogenetics, ethnic differences in drug response and drug regulation. In: Pharmacogenomics in Admixed Populations, ed. Saurez-Kurtz G. Austin (Texas): Landes Bioscience, 2007; 180-197.
13. Temple R, Stockbridge NL. BiDil for heart failure in black patients: The U.S. Food and Drug Administration perspective. Ann Intern Med 2007; 146: 57-62.
14. Ellison GT, Kaufman JS, Head RF, Martin PA, Kahn JD. Flaws in the U.S. Food and Drug Administration's rationale for supporting the development and approval of BiDil as a treatment for heart failure only in black patients. J Law Med Ethics 2008; 36: 449-457.
15. Adams SS. The discovery of Brufen. Chem Br 1987; 23: 1193-1195.
16. Nakae K, Yamamoto S, Shigematsu I, Kono R. Relation between subacute myelo-optic neuropathy (SMON) and clioquinol: a nationwide survey. Lancet 1973; 1: 171-173.
17. Shah RR. Thalidomide, drug safety and early drug regulation in the UK. Adverse Drug React Toxicol Rev 2001; 20: 199-255.
18. Wadia NH. SMON as seen from Bombay. Acta Neurol Scand Suppl 1984; 100: 159-164.
19. European Medicines Agency. Clinical trials submitted in marketing authorisation applications to the EMA (EMA/INS/GCP/154352/2010). EMA. London, 5 November 2010. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/12/WC500016819.pdf [last accessed 20 February 2012].
20. Bernard S, Neville KA, Nguyen AT, Flockhart DA. Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population: clinical implications. Oncologist 2006; 11: 126-135.
21. Evelyn B, Toigo T, Banks D, Pohl D, Gray K, Robins B, Ernat J. Participation of racial/ethnic groups in clinical trials and race-related labeling: a review of new molecular entities approved 1995-1999. J Natl Med Assoc 2001; 93: (12 Suppl.): 18S-24S.
22. Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA 2004; 291: 2720-2726.
23. Begaud B. The liver as the target organ for idiosyncratic reactions. In: Idiosyncratic Drug Reactions: Impact on Drug Development and Clinical Use after Marketing, eds Naranjo CA, Jones JK. Amsterdam: Elsevier Science Publishers BV, 1990; 85-98.
24. Pillans PI. Drug associated hepatic reactions in New Zealand: 21 years experience. N Z Med J 1996; 109: 315-319.
25. Graham DJ, Green L, Senior JR, Nourjah P. Troglitazone-induced liver failure: a case study. Am J Med 2003; 114: 299-306.
26. Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993; 270: 2590-2597.
27. Zeltser D, Justo D, Halkin A, Prokhorov V, Heller K, Viskin S. Torsade de pointes due to noncardiac drugs: most patients have easily identifiable risk factors. Medicine (Baltimore) 2003; 82: 282-290.
28. Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME. Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clin Proc 2003; 78: 1479-1487.
29. Mason JW, Ramseth DJ, Chanter DO, Moon TE, Goodman DB, Mendzelevski B. Electrocardiographic reference ranges derived from 79, 743 ambulatory subjects. J Electrocardiol 2007; 40: 228-234.
30. Macfarlane PW, McLaughlin SC, Devine B, Yang TF. Effects of age, sex, and race on ECG interval measurements. J Electrocardiol 1994; 27: (Suppl.): 14-19.
31. Mansi IA, Nash IS. Ethnic differences in electrocardiographic intervals and axes. J Electrocardiol 2001; 34: 303-307.
32. Rautaharju PM, Prineas RJ, Kadish A, Larson JC, Hsia J, Lund B. Normal standards for QT and QT subintervals derived from a large ethnically diverse population of women aged 50 to 79 years (the Women's Health Initiative [WHI]). Am J Cardiol 2006; 97: 730-737.
33. Kim JW, Hong KW, Go MJ, Kim SS, Tabara Y, Kita Y, Tanigawa T, Cho YS, Han BG, Oh B. A common variant in SLC8A1 is associated with the duration of the electrocardiographic QT interval. Am J Hum Genet 2012; 91: 180-184.
34. Florian JA, Tornøe CW, Brundage R, Parekh A, Garnett CE. Population pharmacokinetic and concentration-QTc models for moxifloxacin: pooled analysis of 20 thorough QT studies. J Clin Pharmacol 2011; 51: 1152-1162.
35. Grosjean P, Urien S. Reevaluation of moxifloxacin pharmacokinetics and their direct effect on the QT interval. J Clin Pharmacol 2012; 52: 329-338.
36. Eap CB, Crettol S, Rougier JS, Schläpfer J, Sintra Grilo L, Déglon JJ, Besson J, Croquette-Krokar M, Carrupt PA, Abriel H. Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin Pharmacol Ther 2007; 81: 719-728.
37. Makita N, Horie M, Nakamura T, Ai T, Sasaki K, Yokoi H, Sakurai M, Sakuma I, Otani H, Sawa H, Kitabatake A. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation 2002; 106: 1269-1274.
38. Kannankeril PJ, Roden DM, Norris KJ, Whalen SP, George AL Jr, Murray KT. Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in first-degree relatives. Heart Rhythm 2005; 2: 134-140.
39. Shimizu T, Ochiai H, Asell F, Shimizu H, Saitoh R, Hama Y, Katada J, Hashimoto M, Matsui H, Taki K, Kaminuma T, Yamamoto M, Aida Y, Ohashi A, Ozawa N. Bioinformatics research on inter-racial difference in drug metabolism. 1. Analysis on frequencies of mutant alleles and poor metabolizers on CYP2D6 and CYP2C19. Drug Metab Pharmacokinet 2003; 18: 48-70.
40. Ozawa S, Soyama A, Saeki M, Fukushima-Uesaka H, Itoda M, Koyano S, Sai K, Ohno Y, Saito Y, Sawada J. Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1. Drug Metab Pharmacokinet 2004; 19: 83-95.
41. Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP. Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics 2004; 5: 895-931.
42. Yasuda SU, Zhang L, Huang S-M. The role of ethnicity in variability in response to drugs: focus on clinical pharmacology studies. Clin Pharmacol Ther 2008; 84: 417-423.
43. Ackerman MJ, Splawski I, Makielski JC, Tester DJ, Will ML, Timothy KW, Keating MT, Jones G, Chadha M, Burrow CR, Stephens JC, Xu C, Judson R, Curran ME. Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing. Heart Rhythm 2004; 1: 600-607.
44. Koo SH, Ho WF, Lee EJ. Genetic polymorphisms in KCNQ1, HERG, KCNE1 and KCNE2 genes in the Chinese, Malay and Indian populations of Singapore. Br J Clin Pharmacol 2006; 61: 301-308.
45. van Norstrand DW, Tester DJ, Ackerman MJ. Over-representation of the proarrhythmic, sudden death predisposing sodium channel polymorphism, S1103Y, in a population-based cohort of African American sudden infant death syndrome. Heart Rhythm 2008; 5: 712-715.
46. Liu JF, Goldenberg I, Moss AJ, Shimizu W, Wilde AA, Hofman N, McNitt S, Zareba W, Miyamato Y, Robinson JL, Andrews ML. Phenotypic variability in Caucasian and Japanese patients with matched LQT1 mutations. Ann Noninvasive Electrocardiol 2008; 13: 234-241.
47. Jamshidi Y, Nolte IM, Dalageorgou C, Zheng D, Johnson T, Bastiaenen R, Ruddy S, Talbott D, Norris KJ, Snieder H, George AL, Marshall V, Shakir S, Kannankeril PJ, Munroe PB, Camm AJ, Jeffery S, Roden DM, Behr ER. Common variation in the NOS1AP gene is associated with drug-induced QT prolongation and ventricular arrhythmia. J Am Coll Cardiol 2012; May 23. 60: 841-850. [Epub ahead of print].
48. Olatunde A, Evans DAP. Blood quinidine levels and cardiac effects in white British and Nigerian subjects. Br J Clin Pharmacol 1982; 14: 513-518.
49. Shin JG, Kang WK, Shon JH, Arefayene M, Yoon YR, Kim KA, Kim DI, Kim DS, Cho KH, Woosley RL, Flockhart DA. Possible interethnic differences in quinidine-induced QT prolongation between healthy Caucasian and Korean subjects. Br J Clin Pharmacol 2007; 63: 206-215.
50. Wheeler W, Olbertz J, Azzam S, DeGroot B, Reinbolt E, Clark K. Investigating ethnic differences in QTcF response to moxifloxacin in a randomized, double-blind study (abstract PII-13). Clin Pharmacol Ther 2011; 89: (Suppl. 1): S42.
51. Malik M, Hnatkova K, Schmidt A, Smetana P. Electrocardiographic Q. Tc changes due to moxifloxacin infusion. J Clin Pharmacol 2009; 49: 674-683.
52. Kannankeril PJ, Norris KJ, Carter S, Roden DM. Factors affecting the degree of QT prolongation with drug challenge in a large cohort of normal volunteers. Heart Rhythm 2011; 8: 1530-1534.
53. Yan LK, Zhang J, Ng MJ, Dang Q. Statistical characteristics of moxifloxacin-induced QTc effect. J Biopharm Stat 2010; 20: 497-507.
54. Poordad F, Zeldin G, Harris SI, Ke J, Xu L, Mayers D, Zhou XJ. Absence of effect of telbivudine on cardiac repolarization: results of a thorough QT/QTc study in healthy participants. J Clin Pharmacol 2009; 49: 1436-1446.
55. Mason JW, Florian JA Jr, Garnett CE, Moon TE, Selness DS, Spaulding RR. Pharmacokinetics and pharmacodynamics of three moxifloxacin dosage forms: implications for blinding in active-controlled cardiac repolarization studies. J Clin Pharmacol 2010; 50: 1249-1259.
56. Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 2003; 73: 292-303.
57. c studies in healthy volunteers. Br J Clin Pharmacol 2010; 69: 391-400.
58. c interval assessed in both healthy Japanese and Caucasian subjects. Br J Clin Pharmacol 2012; 73: 455-459.
59. Salvi V, Karnad DR, Panicker GK, Natekar M, Hingorani P, Kerkar V, Ramasamy A, de Vries M, Zumbrunnen T, Kothari S, Narula D. Comparison of 5 methods of QT interval measurements on electrocardiograms from a thorough QT/QTc study: effect on assay sensitivity and categorical outliers. J Electrocardiol 2011; 44: 96-104.
60. Darpo B, Fossa AA, Couderc JP, Zhou M, Schreyer A, Ticktin M, Zapesochny A. Improving the precision of QT measurements. Cardiol J 2011; 18: 401-410.
61. Wadem EF, Haigney MC. The thorough QT study: let us be precise. Cardiol J 2011; 18: 341-342.
62. Natekar M, Hingorani P, Gupta P, Karnad DR, Kothari S, de Vries M, Zumbrunnen T, Narula D. Effect of number of replicate electrocardiograms recorded at each time point in a thorough QT study on sample size and study cost. J Clin Pharmacol 2011; 51: 908-914.
63. c study' following ICH E14 using various QT correction methods. Br J Clin Pharmacol 2009; 68: 435-446.
64. Garnett CE, Zhu H, Malik M, Fossa AA, Zhang J, Badilini F, Li J, Darpö B, Sager P, Rodriguez I. Methodologies to characterize the QT/corrected QT interval in the presence of drug-induced heart rate changes or other autonomic effects. Am Heart J 2012; 163: 912-930.
65. Food and Drug Administration. New Drug Evaluation Guidance Document: Refusal to File. FDA, Rockville, Maryland, USA, 12 July 1993. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM080561.pdf [last accessed 20 February 2012].
66. International Conference on Harmonisation. Dose-response information to support drug registration. ICH, Geneva, 10 March 1994. Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E4/Step4/E4_Guideline.pdf [last accessed 20 February 2012].
67. Food and Drug Administration. Investigational New Drug Applications and New Drug Applications. FDA, Rockville, Maryland, USA, 11 February 1998. Available at: http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm120254.htm [last accessed 20 February 2012].
68. International Conference on Harmonisation. Ethnic factors in the acceptability of foreign clinical data. ICH, Geneva, 5 February 1998. Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E5_R1/Step4/E5_R1__Guideline.pdf [last accessed 20 February 2012].
69. International Conference on Harmonisation. Pharmacovigilance planning. ICH, Geneva, 18 November 2004. Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2E/Step4/E2E_Guideline.pdf [last accessed 20 February 2012].
70. Food and Drug Administration. Guidance for Industry: Collection of Race and Ethnicity Data in Clinical Trials. FDA, Rockville, Maryland, USA, September 2005. Available at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126396.pdf [last accessed 20 February 2012].
71. European Medicines Agency. Reflection paper on the extrapolation of results from clinical trials conducted outside the EU to the EU-population (EMEA/CHMP/EWP/692702/2008). EMA, London, 22 October 2009. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/11/WC500013468.pdf [last accessed 20 February 2012].