Clinical therapeutics | 2019
Effects of Celecoxib on the QTc Interval: A Thorough QT/QTc Study.
Abstract
PURPOSE\nCelecoxib is a selective cyclooxygenase-2 inhibitor widely used in patients with osteoarthritis and rheumatoid arthritis. Recently, nonclinical data on the inhibition of human ether-à-go-go-related gene potassium channels by celecoxib were reported, but there is no compelling evidence for this finding in humans. The aim of this study was to assess the potential effects of celecoxib on cardiac repolarization by conducting a thorough QT study, which was designed in compliance with the related guidelines.\n\n\nMETHODS\nThis randomized, open-label, positive- and negative-controlled, crossover clinical study was conducted in healthy male and female subjects. Each subject received, in 1 of 4 randomly assigned sequences, all of the following 3 interventions: celecoxib 400\xa0mg once daily for 6 days; a single dose of moxifloxacin 400\xa0mg, which served as a positive control to assess the assay sensitivity; and water without any drug, which served as a negative control. Serial 12-lead ECG and blood samples for pharmacokinetic analysis were collected periodically over 24\xa0h. Individually RR-corrected QT intervals (QTcI) and Fridericia method-corrected QT intervals (QTcF) were calculated and evaluated.\n\n\nFINDINGS\nTwenty-eight subjects were allocated to 1 of the 4 intervention sequences. The largest time-matched mean effects of celecoxib on the QTcI and QTcF were <5\xa0ms, and the upper bounds of the 1-sided 95% CIs of those values did not exceed 10\xa0ms. Moreover, none of the subjects had an absolute QTcI value of >450\xa0ms or a change from baseline in QTcI of >60\xa0ms after multiple administrations of celecoxib. The QTcI did not show a positive correlation with celecoxib concentrations in the range up to ~2700\xa0μg/L. The overall effects of moxifloxacin on the QTcI and QTcF were enough to establish assay sensitivity. No serious adverse events were reported, with a total of 11 AEs reported in 8 subjects.\n\n\nIMPLICATIONS\nCelecoxib caused no clinically relevant increase in the QT/QTc interval at the maximum dose level used in current practice settings. ClinicalTrials.gov identifier: NCT03822520 (Clin Ther. 2019; 41:XXX-XXX) © 2019 Elsevier Inc.