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

Journal of Clinical Pharmacology

Volumn 46, Issue 5, 2006, Pages 498-507

  Darpo, Borje ^a,b   Nebout, Thierry ^c   Sager, Philip T ^d,e  

^a Daiichi Medical Research   (United Kingdom)

^b KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^c INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

^d ASTRAZENECA   (United Kingdom)

^e UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY   (United States)

Author keywords

ECG methodology; ICH E14; QT prolongation; Thorough QT study

Indexed keywords

ALFUZOSIN; AMIODARONE; MOXIFLOXACIN; VARDENAFIL;

ALGORITHM; ANALYTIC METHOD; CARDIOVASCULAR RISK; CLINICAL EXAMINATION; DEVELOPMENTAL STAGE; DRUG APPROVAL; DRUG DOSE REGIMEN; DRUG INDUSTRY; DRUG POTENCY; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; DRUG USE; DRUG WITHDRAWAL; ELECTROCARDIOGRAPHY MONITORING; HEALTH CARE ORGANIZATION; HEALTH PROGRAM; HEART PROARRHYTHMIA; HUMAN; MEDICAL DOCUMENTATION; MEDICAL EXPERT; METHODOLOGY; NONHUMAN; NORMAL VALUE; PRACTICE GUIDELINE; PROSTATE HYPERTROPHY; QT PROLONGATION; REGISTRATION; REVIEW; RISK ASSESSMENT; SEXUAL DYSFUNCTION; STATISTICAL ANALYSIS; TREATMENT WITHDRAWAL;

ANIMALS; ARRHYTHMIA; ARRHYTHMIAS, CARDIAC; CONTROLLED CLINICAL TRIALS; CONTROLLED CLINICAL TRIALS AS TOPIC; CROSS-OVER STUDIES; DRUG APPROVAL; DRUG EVALUATION, PRECLINICAL; DRUG INDUSTRY; DRUGS, INVESTIGATIONAL; HUMANS; INTERNATIONAL COOPERATION; LONG QT SYNDROME;

EID: 33645790554     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270006286436     Document Type: Review

References (44)

1. Committee for Proprietary Medicinal Products. Points to Consider: The Assessment of the Potential for QT Interval Prolongation by Non-Cardiovascular Medicinal Products. London, United Kingdom: Committee for Proprietary Medicinal Products; December 17, 1997.
2. Shall R. Withdrawal of terodiline: a tale of two toxicities. In: Mann RD, Andrews EB, eds. Pharmacovigilance. London, United Kingdom: John Wiley & Sons; 2002:135-154.
3. Shall RR. The significance of QT interval in drug development. Br J Clin Pharmacol. 2002;54:188-202.
4. Pratt CM, Ruberg S, Morganroth J, et al. Dose-response relation between terfenadine (Seldane) and the QTc interval on the scalar electrocardiogram: distinguishing a drug effect from spontaneous variability. Am Heart J. 1996;131:472-480.
5. Wysowski DK, Bacsanyi J. Cisapride and fatal arrhythmia [letter]. N Eng J Med. 1996;335:290-291.
6. Yap YG, Camm AJ. Arrhythmogenic mechanisms of non-sedating antihistamines. Clin Exp Allergy. 1999;29:174-181.
7. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart. 2003;89:1363-1372.
8. Darpo B. Spectrum of drugs prolonging the QT interval and the incidence of torsades de pointes. Eur Heart J. 2001;3(suppl K):70-80.
9. Shah RR. Drug-induced prolongation of the QT interval: why the regulatory concern? Fundam Clin Pharmacol. 2002;16:119-124.
10. Shall 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.
11. Barbey JT, Lazzara R, Zipes DP. Spontaneous adverse event reports of serious ventricular arrhythmias, QT prolongation, syncope, and sudden death in patients treated with cisapride. J Cardiovasc Pharmacol Ther. 2002;7:65-76.
12. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs: E14. Geneva, Switzerland: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2005. Available at http://www.ich.org/LOB/media/MEDIA1476.pdf.
13. Antzelevitch C. Cellular, molecular and pharmacologic mechanisms underlying drug-induced cardiac arrhtyhmogenesis. In: Morganroth J, Gussak I, eds. Cardiac Safety of Noncardiac Drugs: Practical Guidelines for Clinical Research and Drug Development. Totowa, NJ: Humana Press.
14. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The Non-Clinical Evaluation of The Potential For Delayed Ventricular Repolarization (Qt Interval Prolongation) by Human Pharmaceuticals: S7B. Geneva, Switzerland: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2005. Available at http://www.ich.org/LOB/media/MEDIA2192.pdf.
15. Demolis JL, Charransol A, Funck-Brentano C, Jaillon P. Effects of a single oral dose of sparfloxacin on ventricular repolarization in healthy volunteers. Br J Clin Pharmacol. 1996;41:499-503.
16. Demolis JL, Kubitza D, Tenneze L, Funck-Brentano C. Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects. Clin Pharmacol Ther. 2000;68:658-666.
17. Honig PK, Wortham DC, Zamani K, Conner DP, Mullin JC, Cantilena LR. Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences. JAMA. 1993;269:1513-1518.
18. Kivisto KT, Lilja JJ, Backman JT, Neuvonen PJ. Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride. Clin Pharmacol Ther. 1999;66:448-453.
19. van Haarst AD, van 't Klooster GA, van Gerven JM, et al. The influence of cisapride and clarithromycin on QT intervals in healthy volunteers. Clin Pharmacol Ther. 1998;64:542-546.
20. Agin M, Kazierad DJ, Abel R, et al. Assessing QT variability in healthy volunteers. In press.
21. US Food and Drug Administration. FDA review for Uroxatral (alfuzocin HCl tablets). May 29, 2003. Available at: http://www.fda.gov/ohrms/dockets/ac/03/ briefing/3956B1_01_FDA-alfuzosin.pdf.
22. 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.
23. White CM, Grant EM, Quintiliani R. Moxifloxacin does increase the corrected QT interval. Clin Infect Dis. 2001;33:1441-1444.
24. Azie NE, Adams G, Darpo B, et al. Comparing methods of measurement for detecting drug-induced changes in the QT interval: implications for thoroughly conducted ECG studies. Ann Noninvasive Electrocardiol. 2004;9:166-174.
25. Sarapa N, Morganroth J, Couderc JP, et al. Electrocardiographic identification of drug-induced QT prolongation: assessment by different recording and measurement methods. Ann Noninvasive Electrocardiol. 2004;9:48-57.
26. Guomo S, De Caprio L, Di Palma A, et al. Influence of autonomic tone on QT interval duration. Cardiologia. 1997;42:1071-1076.
27. Diedrich A, Jordan J, Shannon JR, Robertson D, Biaggioni I. Modulation of QT interval during autonomic nervous system blockade in humans. Circulation. 2002;106:2238-2243.
28. Frederiks J, Swenne CA, Kors JA, et al. Within-subject electrocardiographic differences at equal heart rates: role of the autonomic nervous system. Pflugers Arch. 2001;441:717-724.
29. Piccirillo G, Cacciafesta M, Lionetti M, et al. Influence of age, the autonomic nervous system and anxiety on QT-interval variability. Clin Sci (Lond). 2001;101:429-438.
30. Demolis JL, Vacheron F, Cardus S, Funck-Brentano C. Effect of single and repeated oral doses of telithromycin on cardiac QT interval in healthy subjects. Clin Pharmacol Ther. 2003;73:242-252.
31. Nagy D, DeMeersman R, Gallagher D, et al. QTc interval (cardiac repolarization): lengthening after meals. Obes Res. 1997;5:531-537.
32. Darpo B, Agin M, Kazierad DJ, et al. Man versus machine: is there an optimal method for QT measurements in thorough QT studies? In press.
33. Dota C, Skallefell B, Edvardsson N, Fager G. Computer-based analysis of dynamic QT changes: toward high precision and individual rate correction. Ann Noninvasive Electrocardiol. 2002;7:289-301.
34. Dota CD, Edvardsson N, Schutzer KM, et al. Inter- and intraday variability in major electrocardiogram intervals and amplitudes in healthy men and women. Pacing Clin Electrophysiol. 2003;26:361-366.
35. Houltz B, Darpo B, Edvardsson N, et al. Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study. Pacing Clin Electrophysiol. 1998;21:1044-1057.
36. Malik M, Camm AJ. Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling. Drug Saf. 2001;24:323-351.
37. Malik M. Problems of heart rate correction in the assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol. 2001;12:412-420.
38. Malik M, Farbom P, Batchvarov V, Hnatkova K, Camm AJ. Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval. Heart. 2002;87:220-228.
39. Bazett HC. An analysis of time relations of electrocardiograms. Heart. 1920;353-367.
40. Extramiana F, Maison-Blanche P, Cabanis MJ, Ortemann-Renon C, Beaufils P, Leenhardt A. Clinical assessment of drug-induced QT prolongation in association with heart rate changes. Clin Pharmacol Ther. 2005;77:247-258.
41. Malik M. Assessment of drug-induced QT prolongation: to bin or not to bin? Clin Pharmacol Ther. 2005;77:241-246.
42. Patterson S, Agin M, Anziano R, et al. Investigating drug-induced QT and QTc Prolongation in the clinic: a review of statistical design and analysis considerations. Report from pharmaceutical Research and Manufacturer of America QT statistics expert team. In press.
43. Hanrahan JP, Choo PW, Carlson W, Greineder D, Faich GA, Platt R. Terfenadine-associated ventricular arrhythmias and QTc interval prolongation: a retrospective cohort comparison with other antihistamines among members of a health maintenance organization. Ann Epidemiol. 1995;5:201-209.
44. Walker AM, Szneke P, Weatherby LB, et al. The risk of serious cardiac arrhythmias among cisapride users in the United Kingdom and Canada. Am J Med. 1999;107:356-362.