HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Darpo, B. Articles by Sager, P. T. Search for Related Content PubMed PubMed Citation Articles by Darpo, B. Articles by Sager, P. T. Social Bookmarking                         What's this?

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

From the Daiichi Medical Research, London, United Kingdom (Dr Darpo); the Department of Cardiology, Karolinska Hospital, Stockholm, Sweden (Dr Darpo); the Medical Sciences, Institut de Recherches Internationales SERVIER, Paris, France (Dr Nebout); Cardiovascular Research, AstraZeneca LP, Wilmington, Delaware (Dr Sager); and the University of Medicine and Dentistry of New Jersey, Newark, New Jersey (Dr Sager).

Proarrhythmias due to drug-induced QT prolongation are the second most common cause for drug withdrawal and have caused increasing concern. Two new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines were recently endorsed in which nonclinical (S7B) and clinical (E14) methodologies are discussed and guidance is given to the industry. This commentary describes the key components of the E14 document, the impact of nonclinical testing on the clinical program, the thorough QT study, and the impact of its result on late-stage development. The studies described in S7B and E14 will contribute to a better understanding of the link between nonclinical assays and QT prolongation in humans. Differences in interpretation among individual regulators in the major regions with respect to measures proposed in the E14 guideline might impact regional regulatory decisions. These differences include the value of nonclinical assays for the subsequent clinical testing and how predictive a negative thorough QT study result is for proarrhythmic risk in patients.

Key Words: QT prolongation • ICH E14 • thorough QT study • ECG methodology

Address for reprints: Borje Darpo, MD, PhD, Daiichi Medical Research, 76 Shoe Lane, London EC4A 3JB United Kingdom; e-mail: borje.darpo{at}dmr.daiichius.com.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				F. Poordad, G. Zeldin, S. I. Harris, J. Ke, L. Xu, D. Mayers, and X.-J. Zhou Absence of Effect of Telbivudine on Cardiac Repolarization: Results of a Thorough QT/QTc Study in Healthy Participants J. Clin. Pharmacol., December 1, 2009; 49(12): 1436 - 1446. [Abstract] [Full Text] [PDF]

				D. J. Chatterjee, N. Khutoryansky, M. Zdravkovic, C. R. Sprenger, and J. S. Litwin Absence of QTc Prolongation in a Thorough QT Study With Subcutaneous Liraglutide, a Once-Daily Human GLP-1 Analog for Treatment of Type 2 Diabetes J. Clin. Pharmacol., November 1, 2009; 49(11): 1353 - 1362. [Abstract] [Full Text] [PDF]

				N. Sarapa, S. F. Francom, S. M. Azzam, P. K. Wickremasingha, and B. Tyl Detection of Clinically Significant QTc Prolongation in Phase I Studies in Healthy Participants: Comparison of 2 Semiautomated QT Measurement Methods J. Clin. Pharmacol., January 1, 2009; 49(1): 103 - 108. [Full Text] [PDF]

				M. Peeters, K. Janssen, T. N Kakuda, M. Scholler-Gyure, R. Lachaert, R. M. Hoetelmans, B. Woodfall, and G. De Smedt Etravirine Has No Effect on QT and Corrected QT Interval in HIV-Negative Volunteers Ann. Pharmacother., June 1, 2008; 42(6): 757 - 765. [Abstract] [Full Text] [PDF]

				M. M. Hutmacher, S. Chapel, M. A. Agin, J. C. Fleishaker, and R. L. Lalonde Performance Characteristics for Some Typical QT Study Designs Under the ICH E-14 Guidance J. Clin. Pharmacol., February 1, 2008; 48(2): 215 - 224. [Abstract] [Full Text] [PDF]

				D. M. Roden, P. Kannankeril, and D. Darbar On the relationship among QT interval, atrial fibrillation, and torsade de pointes Europace, September 1, 2007; 9(suppl_4): iv1 - iv3. [Full Text] [PDF]

				B. Darpo Detection and reporting of drug-induced proarrhythmias: room for improvement Europace, September 1, 2007; 9(suppl_4): iv23 - iv36. [Abstract] [Full Text] [PDF]