How to Successfully Generate an Alternative Approach to a Thorough QT Study: GLPG1972 as an Example

Claudia Meyer; Ines Dierick; Glenn Gauderat; Jurgen Langenhorst; Céline Sarr; Emilie Leroux; Marylore Chenel; Sylvain Fouliard; Paul Passier

doi:10.1002/cpt.2596

How to Successfully Generate an Alternative Approach to a Thorough QT Study: GLPG1972 as an Example

Clin Pharmacol Ther. 2023 Feb;113(2):310-320. doi: 10.1002/cpt.2596. Epub 2022 Apr 27.

Authors

Claudia Meyer¹, Ines Dierick², Glenn Gauderat³, Jurgen Langenhorst⁴, Céline Sarr⁴, Emilie Leroux³, Marylore Chenel⁴, Sylvain Fouliard³, Paul Passier¹

Affiliations

¹ Galapagos B.V., Leiden, The Netherlands.
² Galapagos NV, Mechelen, Belgium.
³ Translational Medicine Division, Servier, Suresnes, France.
⁴ Pharmetheus A.B., Uppsala, Sweden.

Abstract

During development of a drug, the requirement of evaluating the proarrhythmic risk and delayed repolarization needs to be fulfilled. Would it be possible to create an alternative to a thorough QT (TQT) study or is there a need to perform a dedicated TQT study? How is an alternative approach generated, what information is available, and which instructions are considered missing today to generate such an approach? This tutorial describes the considerations and path followed to create an early and feasible alternative to a TQT study using experience-based insights from a successful application to the US Food and Drug Administration for GLPG1972, an ADAMTS-5 inhibitor, and discusses the approach used in light of the current guidelines and literature.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Electrocardiography
Humans
Long QT Syndrome* / chemically induced
Long QT Syndrome* / diagnosis
Pharmaceutical Preparations
United States
United States Food and Drug Administration

Substances

Pharmaceutical Preparations