Effects of Celecoxib on the QTc Interval: A Thorough QT/QTc Study |
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| Affiliation: | 1. Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea;2. Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea;1. Department of Adult Critical Care Medicine, Tainan Sin-Lau Hospital, Tainan, Taiwan;2. Graduate Institute of Medical Sciences, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan;3. Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;4. Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan;5. Department of Medicine, Chi-Mei Medical Center, Tainan, Taiwan;6. Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;7. Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;1. Purdue University College of Pharmacy, West Lafayette, IN, USA;2. Indiana University Health Arnett Nephrology, Lafayette, IN, USA;1. Department of Immunology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic;2. Department of Pediatrics, Thomayer’s Hospital, Prague, Czech Republic and 1st Faculty of Medicine, Charles University, Prague, Czech Republic;3. Institute of Clinical Immunology and Allergy, University Hospital Hradec Kralove, Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic;4. Centre of Immunology and Microbiology, Regional Institute of Public Health, Usti nad Labem, Czech Republic;5. Department of Immunology and Allergy, Public Health Institute Ostrava, Ostrava, Czech Republic;6. Department of Clinical Immunology Allergy, St Annés University Hospital, Brno, Czech Republic;7. Faculty of Medicicne, Masaryk University, Brno, Czech Republic;8. Institute of Immunology 1st Medical Faculty, Charles University, Prague, Czech Republic;9. Allergy and Clinical Immunology, Regional Hospital in Ceske Budejovice, Czech Republic;10. Department of Clinical Biochemistry, Haematology and Immunology, Na Homolce Hospital, Prague, Czech Republic;11. Department of Pediatrics, University Hospital Hradec Kralove, Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic;12. CSL Behring s.r.o, Prague, Czech Republic;13. CSL Behring AG, Bern, Switzerland |
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| Abstract: | PurposeCelecoxib 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.MethodsThis 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 mg once daily for 6 days; a single dose of moxifloxacin 400 mg, 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 h. Individually RR-corrected QT intervals (QTcI) and Fridericia method–corrected QT intervals (QTcF) were calculated and evaluated.FindingsTwenty-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 ms, and the upper bounds of the 1-sided 95% CIs of those values did not exceed 10 ms. Moreover, none of the subjects had an absolute QTcI value of >450 ms or a change from baseline in QTcI of >60 ms after multiple administrations of celecoxib. The QTcI did not show a positive correlation with celecoxib concentrations in the range up to ~2700 μg/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.ImplicationsCelecoxib caused no clinically relevant increase in the QT/QTc interval at the maximum dose level used in current practice settings. ClinicalTrials.gov identifier: NCT03822520. |
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| Keywords: | celecoxib proarrhythmic potential QT prolongation thorough QT/QTc study |
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