{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T19:12:34Z","timestamp":1778008354715,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T00:00:00Z","timestamp":1672617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>This thorough QT\/QTc (TQT) study was conducted to evaluate the risk of QT prolongation for verinurad when combined with allopurinol. Verinurad is a novel, urate anion exchanger 1 inhibitor that reduces serum urate levels by promoting urinary excretion of uric acid. It is co\u2010administered with a xanthine oxidase inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The TQT study (NCT04256629) was a randomized, placebo\u2010controlled, double\u2010blind, three\u2010period, crossover study, conducted in healthy volunteers. A total of 24 participants received single doses of verinurad 24\u2009mg extended release, 40\u2009mg immediate release formulation (both co\u2010administered with allopurinol 300\u2009mg), and matching placebos. The primary endpoint was baseline\u2010 and placebo\u2010adjusted Fridericia\u2010corrected QTcF interval (\u0394\u0394QTcF) at the concentration of interest. A prespecified linear mixed\u2010effects concentration\u2013QTc model was used to estimate the primary endpoint. Time\u2010matched 12\u2010lead digital electrocardiograms and plasma concentrations were measured at baseline and up to 48\u2009h after dose in each participant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Estimated \u0394\u0394QTcF at the highest clinically relevant scenario (76\u2009ng\/mL) was \u22122.7\u00a0msec (90% confidence interval [CI]: \u22124.6, \u22120.8). Furthermore, the upper 90% \u0394\u0394QTcF CI was estimated to be below 10\u00a0msec at all observed verinurad concentrations. Supratherapeutic verinurad dose was used to achieve exposures eightfold higher than the highest clinically relevant exposure, thus waiving the need for positive control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>As the effect on \u0394\u0394QTcF was below the threshold for regulatory concern (10\u00a0msec) at the supratherapeutic exposure, it can be concluded that verinurad and allopurinol treatment does not induce QTcF prolongation at the highest clinically relevant exposures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15637","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T13:45:45Z","timestamp":1670852745000},"page":"1747-1755","source":"Crossref","is-referenced-by-count":2,"title":["Verinurad does not prolong QTc interval: a thorough QT study using concentration\u2013QTc modelling"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-5243","authenticated-orcid":false,"given":"Joanna","family":"Parkinson","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Dota","sequence":"additional","affiliation":[{"name":"Cardiovascular Safety Center of Excellence and Safety Knowledge Group, Global Patient Safety, Oncology R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"K\u00e4llgren","sequence":"additional","affiliation":[{"name":"Late\u2010Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&amp;D AstraZeneca  Gothenburg 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Unit Parexel International  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinko","family":"Reki\u0107","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-0278","authenticated-orcid":false,"given":"Susanne","family":"Johansson","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences R&amp;D AstraZeneca  Gothenburg 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Available from:https:\/\/database.ich.org\/sites\/default\/files\/E14_Q%26As_R3_Q%26As.pdf. Published December 10 2015. Accessed December 14 2022."},{"key":"e_1_2_10_17_1","unstructured":"International Council for Harmonisation.The clinical evaluation of QT\/QTc interval. Prolongation and proarrhythmic potential for non\u2010antiarrhytmic drugs E14. Available from:https:\/\/database.ich.org\/sites\/default\/files\/E14_Guideline.pdf"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1119"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen\u20102017\u2010000584"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen\u20102018\u2010000647"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.463"},{"key":"e_1_2_10_22_1","unstructured":"Datapharm.Allopurinol 300mg tablets. Available from:https:\/\/www.medicines.org.uk\/emc\/product\/6006\/smpc. Updated March 9 2022. 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